Zoster Sine Herpete: Definition and Clinical Significance
Zoster sine herpete (ZSH) is varicella-zoster virus (VZV) reactivation that causes dermatomal pain and neurological symptoms without the characteristic vesicular rash, making it a frequently missed diagnosis that requires high clinical suspicion and laboratory confirmation. 1, 2
Clinical Presentation
ZSH manifests through variable symptoms depending on which nerve is affected:
- Neuropathic pain in a dermatomal distribution is the hallmark feature, occurring without any visible skin lesions 1
- Cranial nerve involvement can cause Bell's palsy or Ramsay Hunt syndrome 1
- Visceral involvement may present as chest pain mimicking cardiac disease or abdominal pain 2
- Central nervous system complications include VZV encephalitis and meningitis, which can be life-threatening 1, 2
The absence of the typical vesicular rash makes clinical diagnosis extremely challenging, often leading to misdiagnosis and delayed treatment 1, 2.
Diagnostic Approach
Since visual diagnosis is impossible without rash, laboratory confirmation is essential:
- VZV DNA testing via polymerase chain reaction (PCR) from cerebrospinal fluid when CNS involvement is suspected 2
- Serological testing showing positive VZV IgG and IgM antibodies supports the diagnosis 1, 2
- High clinical suspicion is warranted when patients present with dermatomal pain patterns, especially in older adults or immunocompromised individuals, even without visible lesions 1, 2
Risk Populations
ZSH occurs most commonly in:
- Older adults where declining cell-mediated immunity allows VZV reactivation 3, 4
- Immunocompromised individuals including those on immunosuppressive therapy, with HIV, or undergoing cancer treatment 5, 4
- The lifetime risk of any VZV reactivation (including ZSH) is 20-30% in the general population, with substantially higher rates in these high-risk groups 3, 6
Complications and Sequelae
ZSH can lead to serious complications if not promptly recognized and treated:
- Postherpetic neuralgia (PHN) remains the most common complication, causing debilitating pain that persists for months after the acute episode 6, 7
- VZV encephalitis represents a potentially fatal complication requiring urgent recognition 1
- Stroke has been documented as a severe sequela of ZSH 1
- Misdiagnosis and delayed antiviral treatment significantly increase the risk of these severe outcomes 1
Treatment Considerations
- Antiviral therapy with famciclovir or acyclovir should be initiated as soon as ZSH is suspected, even before laboratory confirmation, given the potential for severe complications 2
- Intravenous acyclovir is required for CNS involvement such as VZV meningitis or encephalitis 2
- Early recognition and treatment may reduce both acute symptoms and the risk of PHN 7
Prevention Through Vaccination
- Recombinant zoster vaccine (Shingrix) is recommended for all adults ≥50 years to prevent both typical herpes zoster and atypical presentations like ZSH 3, 5
- Immunocompromised adults ≥19 years should receive vaccination due to their elevated reactivation risk 5
- The vaccine demonstrates 97.2% efficacy in preventing VZV reactivation, which would include ZSH presentations 8
Critical Clinical Pitfall
The most dangerous pitfall is dismissing dermatomal pain without rash as musculoskeletal or cardiac in origin, particularly when the pain distribution follows a nerve pattern. Always consider ZSH in the differential diagnosis of unexplained dermatomal pain, especially in older or immunocompromised patients, and pursue laboratory confirmation rather than waiting for a rash that will never appear 1, 2.