What is zoster sine herpetica in older adults or those with compromised immune systems?

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 visible skin lesions. 2 The virus still causes the same neurological damage as typical herpes zoster, but the infection remains subclinical at the dermatome level—meaning patients experience the pain without the rash. 2

Who Is at Risk?

Older adults and immunocompromised individuals face the highest risk of ZSH due to declining cell-mediated immunity that allows VZV reactivation. 1

Specific high-risk populations include:

• Adults over 50 years, with dramatically escalating risk after age 60 3
• Immunocompromised patients (HIV, cancer treatment, immunosuppressive therapy) with incidence rates of 40-51 per 1,000 person-years compared to 1.2-4.8 per 1,000 in the general population 3
• Those with hematopoietic stem cell transplantation, hematologic malignancies, or solid organ transplantation 4
• The lifetime risk of any VZV reactivation, including ZSH, is 20-30% in the general population but approaches 50% in those over 85 years 1, 3

Clinical Presentation

The hallmark of ZSH is dermatomal pain in the absence of visible lesions—a presentation that frequently leads to misdiagnosis and delayed treatment. 1, 2

Key clinical features include:

• Neuropathic pain following a dermatomal distribution 2
• Variable neurological symptoms depending on affected nerves (Bell palsy, Ramsay Hunt syndrome) 2
• Potential for severe complications including VZV encephalitis, stroke, and postherpetic neuralgia 2
• No visible rash that would typically confirm the diagnosis 2

Diagnostic Approach

The CDC 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

Maintain high clinical suspicion when patients present with:

• Dermatomal pain patterns in older adults (≥50 years) or immunocompromised individuals, even without visible lesions 1
• Unilateral pain following nerve distributions 2
• Recent history of stress, illness, or immunosuppression 1

Laboratory confirmation is essential and should include VZV DNA testing and/or anti-VZV immunoglobulin (IgG and IgM) antibody testing. 2 Do not rely on clinical diagnosis alone, as the absence of rash makes visual confirmation impossible. 2

Treatment Implications

Misdiagnosis of ZSH and delayed antiviral treatment may lead to severe sequelae, including postherpetic neuralgia and life-threatening complications. 2

Initiate antiviral therapy immediately upon suspicion:

• Valaciclovir 1000 mg three times daily for 7 days or famciclovir 500 mg every 8 hours for 7 days are preferred over aciclovir due to better bioavailability and more convenient dosing 5
• Treatment should begin within 72 hours of symptom onset to reduce pain intensity and prevent complications 5
• Combine antivirals with stepped analgesia: acetaminophen or NSAIDs for mild pain, progressing to opioids for moderate-severe pain 5
• Consider gabapentin (starting 100-300 mg at bedtime, titrating to 300-600 mg three times daily) or nortriptyline (10-25 mg at bedtime) from the acute phase to prevent postherpetic neuralgia 5

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/RZV) demonstrating 97.2% efficacy in preventing VZV reactivation. 1, 3

Critical vaccination points:

• Shingrix is the ONLY appropriate vaccine for immunocompromised patients—live-attenuated Zostavax is absolutely contraindicated due to risk of disseminated VZV infection 3
• Administer a 2-dose series with the second dose 1-2 months after the first for immunocompromised adults (shorter than the standard 2-6 month interval) 3
• Vaccinate patients even with prior herpes zoster history, waiting at least 2 months after acute symptoms resolve 3
• Do not delay vaccination to conduct varicella serology—88-91% of adults have been exposed even without recalled chickenpox 3

Common Pitfalls to Avoid

• Never dismiss dermatomal pain in older or immunocompromised patients simply because no rash is visible—ZSH requires the same urgency as typical herpes zoster 1, 2
• Do not wait for rash development before initiating treatment—in ZSH, the rash will never appear, and delayed treatment increases risk of severe complications 1, 2
• Avoid assuming absence of rash means absence of VZV reactivation—laboratory confirmation is mandatory for diagnosis 2
• Never use live-attenuated Zostavax in immunocompromised patients when vaccinating to prevent future episodes 3