Can herpes simplex infection cause an elevated white blood cell (WBC) count and absolute neutrophil count (ANC)?

Herpes Simplex and Hematologic Changes

Herpes simplex virus (HSV) infection does not typically cause elevated WBC or ANC in immunocompetent hosts; instead, it may actually suppress neutrophil function or induce neutrophil apoptosis, particularly in neonates.

Expected Hematologic Response to HSV

In Immunocompetent Adults

• HSV infections primarily result from viral reactivation and do not characteristically produce leukocytosis or neutrophilia 1
• Unlike bacterial infections, viral infections including HSV typically do not cause significant WBC elevation, as bacterial infections require WBC >14,000 cells/mm³ to be considered significant leukocytosis 2
• HSV-1 infection may actually impair neutrophil chemotaxis and motility rather than increase neutrophil counts 3

Neutrophil Dysfunction Rather Than Elevation

• Patients with recurrent HSV infections demonstrate depressed neutrophil chemotaxis to endotoxin-activated serum, though random migration remains only mildly reduced 3
• HSV-1 infection can induce apoptosis in neonatal neutrophils through Fas/FasL pathway activation, potentially diminishing antiviral response 4
• In adult neutrophils, HSV-1 does not induce the same apoptotic response, but neutrophils do play a role in controlling viral replication rather than proliferating in response to infection 5, 4

When Elevated WBC/ANC Suggests Alternative Diagnosis

Bacterial Superinfection

• If you observe elevated WBC (>14,000 cells/mm³) or ANC with left shift (≥16% bands or ≥1,500 absolute band count), this strongly suggests bacterial superinfection rather than HSV alone 2, 6
• HSV-associated mucosal damage increases risk of bacterial and fungal superinfections, which would then cause the expected neutrophilic response 1
• High WBC and granulocyte counts provide 86-97% specificity for bacterial etiology when values exceed 15.0-20.0 × 10⁹/L 7

Immunocompromised Patients

• In severely immunosuppressed patients (neutropenia with ANC <500 cells/mcL, allogeneic HCT recipients, those on intensive immunosuppressive therapy), HSV reactivation occurs in 60-80% without prophylaxis 1
• However, these patients typically have neutropenia rather than elevated counts, and HSV reactivation occurs during the neutropenic period 1
• The presence of elevated WBC/ANC in this population would more likely indicate bacterial infection or recovery from neutropenia rather than HSV disease 1

Clinical Implications

Diagnostic Approach

• If a patient presents with mucocutaneous HSV lesions AND elevated WBC/ANC, investigate for:
  • Bacterial superinfection of HSV lesions 1
  • Concurrent bacterial infection at another site 2
  • Alternative diagnosis causing the leukocytosis 8

Common Pitfalls to Avoid

• Do not attribute leukocytosis to HSV infection alone in immunocompetent patients; viral infections including HSV do not typically cause significant WBC elevation 7
• Do not assume HSV is controlled if neutrophil counts are normal or elevated; neutrophils help suppress viral replication through mechanisms other than numerical increase 5
• Do not overlook bacterial superinfection in HSV patients with mucosal damage who develop leukocytosis, as this represents increased risk for secondary bacterial and fungal infections 1

When HSV-Related Neutropenia Occurs

• Neonates with HSV-1 infection may experience neutrophil apoptosis and potentially decreased neutrophil counts rather than elevation 4
• Neutrophil depletion in experimental models leads to significantly higher HSV-1 titers and increased mortality, demonstrating that neutrophils control viral replication without necessarily increasing in number 5