What is Zoster Sine Herpete?
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 diagnostic challenge that requires laboratory confirmation rather than clinical observation alone. 1, 2
Clinical Definition and Pathophysiology
ZSH represents an atypical manifestation of herpes zoster where VZV reactivates in cranial nerves, spinal nerves, viscera, or autonomic nerves but fails to produce the typical skin eruption. 2 The virus still travels along nerve pathways and causes tissue damage, but the cutaneous manifestation never appears—the rash you're waiting for will never come. 1
Clinical Presentation
Patients present with dermatomal pain patterns, neurological deficits, or cranial nerve involvement without any visible skin lesions. 1, 2 The symptoms can include:
- Neuropathic pain following a dermatomal distribution, identical to typical herpes zoster pain but without accompanying rash 2
- Bell palsy when facial nerve involvement occurs 2
- Ramsay Hunt syndrome affecting the facial and auditory nerves 2
- Visceral or autonomic symptoms depending on which nerve roots are affected 2
High-Risk Populations
Older adults are at substantially elevated risk due to declining cell-mediated immunity that allows VZV reactivation. 1 The lifetime risk of any VZV reactivation, including ZSH, reaches 20-30% in the general population but approaches 50% in those over 85 years. 1, 3
Immunocompromised individuals face dramatically higher rates, with incidence reaching 40-51 per 1,000 person-years compared to 1.2-4.8 per 1,000 in the general adult population. 3 This includes patients on immunosuppressive therapy, those with HIV, or undergoing cancer treatment. 1
Diagnostic Approach
The Centers for Disease Control and Prevention recommends considering ZSH in the differential diagnosis of unexplained dermatomal pain, especially in older or immunocompromised patients, and pursuing laboratory confirmation rather than waiting for a rash that will never appear. 1
Laboratory diagnosis requires:
- VZV DNA detection through polymerase chain reaction (PCR) testing 2
- Anti-VZV immunoglobulin testing (both IgG and IgM) 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 The key pitfall is dismissing dermatomal pain as musculoskeletal or other causes when ZSH should be in your differential.
Complications and Consequences
Misdiagnosis and delayed antiviral treatment can lead to severe sequelae, including postherpetic neuralgia, VZV encephalitis, and stroke. 2 ZSH causes the same long-term complications as typical herpes zoster, including potentially debilitating postherpetic neuralgia that affects quality of life for months or years. 2
Prevention Strategy
The American College of Immunology recommends vaccination for all adults ≥50 years to prevent both typical herpes zoster and atypical presentations like ZSH, with the recombinant vaccine (Shingrix) demonstrating 97.2% efficacy in preventing VZV reactivation. 1, 3 This is the single most effective intervention for preventing ZSH in at-risk populations.
For immunocompromised adults, administer a 2-dose series with the second dose given 1-2 months after the first dose, which is shorter than the standard interval for immunocompetent adults. 3 Only Shingrix is appropriate for immunocompromised patients—the live-attenuated vaccine is absolutely contraindicated. 3