What is the differential diagnosis for a markedly elevated white blood cell count (~18 ×10⁹/L) with severe abnormal tactile and proprioceptive sensations?

Differential Diagnosis for WBC 18.30 × 10⁹/L with Severe Tactile and Motion Sensations

The combination of leukocytosis (WBC 18.30 × 10⁹/L) with severe abnormal tactile and proprioceptive sensations most urgently suggests Guillain-Barré syndrome (GBS) with concurrent infection, which requires immediate evaluation for both the neurological emergency and the infectious trigger. 1

Immediate Priority: Rule Out Guillain-Barré Syndrome

The severe tactile and motion sensations (proprioceptive abnormalities) are highly concerning for acute inflammatory polyradiculoneuropathy. GBS classically presents with:

• Progressive bilateral weakness with sensory abnormalities including proprioceptive dysfunction 1
• Absent or decreased tendon reflexes at some point in the clinical course 1
• Elevated WBC count may indicate a preceding or concurrent infection (common GBS triggers include Campylobacter jejuni, respiratory viruses, or Zika virus) 1

Critical Actions for GBS Evaluation:

• Perform lumbar puncture for CSF analysis to look for albumino-cytological dissociation (elevated protein with normal cell count), though protein may be normal in the first week in 30-50% of patients 1
• Obtain electrodiagnostic studies to demonstrate sensorimotor polyradiculoneuropathy with reduced conduction velocities, though these may be normal if performed within 1 week of symptom onset 1
• Check for respiratory compromise as GBS can progress to respiratory failure requiring mechanical ventilation 1

Secondary Differential: Infection-Related Causes

Bacterial Infection Assessment:

The WBC of 18.30 × 10⁹/L suggests possible bacterial infection. Order a CBC with manual differential immediately to assess for left shift, as this is the cornerstone test for characterizing leukocytosis. 2

• A left shift of ≥16% band neutrophils increases the likelihood ratio to 4.7 for bacterial infection 2
• An absolute band count of ≥1,500 cells/mm³ increases the likelihood ratio to 14.5 for bacterial infection 2
• A neutrophil percentage >90% increases the likelihood ratio to 7.5 for bacterial infection 2

Specific Infectious Considerations:

• Giant cell arteritis (GCA) can present with elevated inflammatory markers and neurological symptoms, though tactile/proprioceptive changes are atypical. ESR >50 mm/hr has a sensitivity of 78.9% for GCA 1
• Peripheral mycotic aneurysm in IV drug users presents with elevated WBC (frequently present but nonspecific) and can cause neurological symptoms if there is vascular compromise 1

Tertiary Differential: Hematologic Malignancy

While less likely given the acute presentation with sensory symptoms, immediate referral to hematology/oncology is indicated if peripheral smear shows blast cells, immature forms, or dysplastic features. 2

Red Flags for Malignancy:

• Splenomegaly or lymphadenopathy detected on examination requires urgent hematology referral 2, 3
• Constitutional symptoms such as fever, unintentional weight loss, significant fatigue, or night sweats suggest malignancy 3
• Concurrent abnormalities in red blood cell or platelet counts increase suspicion for primary bone marrow disorders 4

Diagnostic Algorithm

Step 1: Neurological Emergency Assessment

1. Assess for progressive weakness, areflexia, and respiratory function 1
2. If GBS suspected, perform CSF analysis and electrodiagnostic studies 1
3. Monitor respiratory status closely as GBS can rapidly progress 1

Step 2: Infection Workup

1. Order CBC with manual differential to calculate absolute neutrophil count and assess for left shift 2
2. Obtain peripheral blood smear to examine WBC morphology and rule out blast cells 2
3. Draw blood cultures before starting antibiotics if systemic symptoms or sepsis signs are present 2
4. Order comprehensive metabolic panel to assess organ function and rule out metabolic causes 2

Step 3: Inflammatory/Vasculitic Evaluation

1. Check ESR and CRP if GCA or other vasculitis is suspected based on age >50 and headache/visual symptoms 1
2. Consider temporal artery examination for thickening, tenderness, or loss of pulse 1

Step 4: Hematologic Assessment

1. Review peripheral smear for blast cells, dysplasia, or immature forms 2
2. If abnormal morphology present, refer urgently to hematology for bone marrow biopsy 2
3. If smear is normal and patient is asymptomatic from hematologic standpoint, repeat CBC in 2-4 weeks 2

Critical Pitfalls to Avoid

• Do not delay CSF analysis and neurological evaluation when sensory abnormalities are prominent, as GBS can progress rapidly to respiratory failure 1
• Do not assume the elevated WBC is solely due to infection without examining the peripheral smear for malignant cells 2
• Do not overlook absolute neutrophil count elevation when assessing for bacterial infection, as left shift can indicate serious infection even with only mildly elevated total WBC 2
• Do not rely on automated differential alone - manual differential is preferred for accurate assessment of cell morphology and to detect dysplasia or immature forms 2
• Do not treat asymptomatic patients with antibiotics based solely on elevated WBC without evidence of infection 2

Most Likely Diagnosis

Given the prominent sensory symptoms (severe tactile and proprioceptive abnormalities), GBS with a concurrent infectious trigger is the most critical diagnosis to exclude immediately, as it represents a neurological emergency requiring ICU-level monitoring and potential plasmapheresis or IVIG therapy. 1 The elevated WBC likely represents the infectious precipitant rather than the primary pathology.