What is the appropriate management for a patient presenting with leukocytosis, paresthesia, abnormal arm sensations, and back tingling, alongside elevated inflammatory markers?

Management of Leukocytosis with Neurological Symptoms

A WBC of 12.7 × 10^9/L with paresthesias, abnormal arm sensations, and back tingling requires urgent evaluation to exclude immune-mediated neuropathy, infection, or inflammatory conditions that could progress to severe neurological compromise.

Initial Diagnostic Approach

Immediate Laboratory Workup

• Complete blood count with manual differential to assess for neutrophilia, lymphopenia, or atypical cells that could indicate infection, inflammation, or hematologic malignancy 1, 2
• Inflammatory markers: ESR and CRP to quantify systemic inflammation; elevations suggest inflammatory or autoimmune processes 3
• Comprehensive metabolic panel including electrolytes, renal function, liver enzymes, calcium, and glucose to identify metabolic derangements 4
• Peripheral blood smear examination to evaluate white blood cell morphology, maturity, and identify toxic granulations or dysplasia 5

Neurological Evaluation Priority

Given the combination of leukocytosis with paresthesias and sensory symptoms, immediate neurologic consultation is warranted to assess for immune-mediated neuropathy, particularly Guillain-Barré syndrome or other immune checkpoint inhibitor-related neuropathies if the patient has cancer history 3.

Key neurological workup includes:

• MRI of spine with or without contrast to rule out compressive lesions and evaluate for nerve root enhancement or thickening 3
• Lumbar puncture with CSF analysis: elevated protein and WBCs may indicate inflammatory neuropathy; send cytology in any patient with cancer 3
• Electrodiagnostic studies (EMG/NCS) to characterize polyneuropathy pattern 3
• Serum antiganglioside antibody testing for Guillain-Barré syndrome subtypes 3

Risk Stratification

Benign vs. Malignant Leukocytosis

A WBC of 12.7 is mild leukocytosis and most commonly represents reactive causes rather than malignancy 1, 2. However, the presence of neurological symptoms shifts the differential toward inflammatory or autoimmune etiologies.

Red flags for malignant causes (requiring hematology referral):

• Concurrent anemia or thrombocytopenia 2
• Immature white blood cells (blasts) on peripheral smear 5
• Fever, weight loss, bruising, or fatigue 3
• Hepatosplenomegaly or lymphadenopathy 2
• WBC >100,000/mm³ (medical emergency due to hyperviscosity risk) 2

Infection vs. Inflammation

Leukocytosis with neurological symptoms raises concern for:

• Infectious causes: meningitis, encephalitis, or systemic infection with secondary neuropathy 1, 2
• Inflammatory/autoimmune: Guillain-Barré syndrome, vasculitis, or immune-mediated neuropathy 3
• Medication-induced: corticosteroids, lithium, or beta-agonists can cause leukocytosis 2

If infection is suspected, obtain blood cultures, urinalysis, chest imaging, and consider lumbar puncture with CSF cultures 3.

Management Algorithm

Grade 1-2 Neurological Symptoms (Mild to Moderate)

Mild paresthesias without motor weakness or functional impairment:

• Screen for reversible causes: diabetic screen, B12, folate, TSH, HIV, serum protein electrophoresis, vasculitic and autoimmune panels 3
• Close observation with repeat assessment within 24-48 hours 6
• Monitor for progression to motor symptoms, facial weakness, dysphagia, or respiratory compromise 3

Grade 3-4 Neurological Symptoms (Severe)

Any motor weakness, rapidly progressive symptoms, facial weakness, dysphagia, or respiratory muscle involvement:

• Immediate hospital admission with capability for ICU-level monitoring 3
• Initiate IVIG (0.4 g/kg/day for 5 days, total 2 g/kg) or plasmapheresis for suspected Guillain-Barré syndrome 3
• Consider pulse corticosteroids (methylprednisolone 1-4 mg/kg/day or 1 g/day for 5 days) for immune-mediated neuropathy, though not typically used for idiopathic Guillain-Barré 3
• Frequent neurochecks and pulmonary function monitoring (negative inspiratory force/vital capacity) 3

Inflammatory Marker Interpretation

Elevated inflammatory markers (ESR/CRP) with leukocytosis:

• CRP >10-20 mg/dL suggests significant systemic inflammation 3
• In diabetic foot infections, elevated inflammatory markers predict worse outcomes and need for amputation 3
• However, isolated elevation of inflammatory markers without clinical symptoms does not warrant treatment escalation 3

Important caveat: Seizures can cause transient leukocytosis, elevated CRP (<6 mg/dL), and fever (<39°C) that resolve within 8 hours without infection 7. If the patient has recent seizure activity, observe for spontaneous resolution before pursuing aggressive workup.

Common Pitfalls to Avoid

• Do not assume mild leukocytosis requires treatment; observation is appropriate for WBC 12.7 without other concerning features 6
• Do not dismiss neurological symptoms as benign in the setting of leukocytosis and elevated inflammatory markers; immune-mediated neuropathies can progress rapidly to respiratory failure 3
• Do not delay neurologic consultation if symptoms are progressive, bilateral, or involve motor weakness 3
• Do not attribute all leukocytosis to infection; physical stress, emotional stress, medications, and inflammatory conditions are common causes 1, 2
• Do not overlook medication history: corticosteroids, lithium, and beta-agonists commonly cause leukocytosis 2

Follow-Up Strategy

If initial workup is unrevealing and symptoms are mild:

• Repeat CBC with differential in 24-48 hours to assess trend 6
• Monitor for development of fever, worsening neurological symptoms, or new systemic signs 6
• No antimicrobial prophylaxis is indicated for mild leukocytosis without fever or infection signs 6

If neurological symptoms worsen or new symptoms develop, immediate escalation to hospital admission and subspecialty consultation is required 3.