What are the risks and prevention strategies for Herpes zoster in older adults over 50 with compromised immune systems due to medical conditions or treatments?

Herpes Zoster Risk in Older Adults Over 50 with Compromised Immune Systems

Risk Profile

Adults over 50 with compromised immune systems face substantially elevated herpes zoster risk, with incidence rates reaching 40-51 per 1,000 person-years in immunocompromised populations compared to 1.2-4.8 per 1,000 in the general adult population. 1, 2

Age-Related Risk Escalation

• Risk increases dramatically starting at age 50, with marked escalation after age 60, reaching lifetime risk approaching 50% in those over 85 years. 2
• The overall lifetime risk in the general population is estimated at 20-30%, but this baseline increases substantially with immunocompromise. 1
• Among immunocompromised patients, herpes zoster incidence increases with age within each disease category (except HIV-infected individuals). 2

Immunocompromise-Specific Risk Factors

• Immunosuppressive medications significantly amplify risk, including glucocorticoids, methotrexate, TNFα antagonists, JAK inhibitors (particularly tofacitinib), abatacept, tocilizumab, and rituximab. 3
• Hematopoietic stem cell transplant recipients experience incidence rates of 40-51 per 1,000 person-years depending on age. 2
• Chronic respiratory diseases like COPD increase herpes zoster risk by 41% compared to healthy controls, with asthma increasing risk by 24%. 4
• Comorbidities including diabetes, rheumatoid arthritis, systemic lupus erythematosus, cancer, and HIV further elevate risk. 5

Complications and Morbidity

• Postherpetic neuralgia (PHN) is the most common and debilitating complication, with immunocompromised individuals at greater risk for severe clinical findings, complications, and recurrence. 6, 7
• Immunocompromised patients have higher mortality rates and atypical presentations requiring laboratory virologic testing. 6
• The 10-year cumulative recurrence risk after an initial episode is 10.3%, and having one episode does not provide reliable protection against future episodes. 5

Prevention Strategies

Vaccination: The Primary Prevention Strategy

The recombinant zoster vaccine (Shingrix/RZV) is the most effective prevention strategy and is specifically recommended for all immunocompromised adults aged 18 years and older, regardless of chickenpox history or prior herpes zoster episodes. 1, 5

Vaccine Selection for Immunocompromised Patients

• Shingrix is the ONLY appropriate vaccine for immunocompromised patients—the live-attenuated vaccine (Zostavax) is absolutely contraindicated due to risk of disseminated VZV infection. 5, 8
• Shingrix contains only a recombinant glycoprotein E subunit with AS01B adjuvant, making it safe for immunosuppressed individuals. 5, 9
• Vaccine efficacy exceeds 90% across all age groups 50 and older, with protection sustained for at least 8-10 years. 5, 8

Dosing Schedule for Immunocompromised Adults

• For immunocompromised adults, administer a 2-dose series with the second dose given 1-2 months after the first dose (shorter than the standard 2-6 month interval for immunocompetent adults). 5, 8
• The minimum interval between doses is 4 weeks; if administered earlier, the dose should be repeated. 8
• Administer intramuscularly. 8

Timing Considerations with Immunosuppressive Therapy

• Ideally, complete the full 2-dose Shingrix series BEFORE starting immunosuppressive therapy to maximize immune response while not yet immunosuppressed. 5
• If urgent therapy initiation is required, administer at least the first dose before starting treatment, with the second dose completed after therapy has begun (though immune response may be somewhat reduced). 5
• For patients already on immunosuppressive therapy, vaccinate immediately—do not delay, as the vaccine remains effective even with reduced immune response. 5
• Consider deferring vaccination until after holding immunosuppressive medication for an appropriate period before and 4 weeks after vaccination when clinically feasible. 5

Special Populations and Scenarios

Patients on Glucocorticoids:

• Concomitant low-dose glucocorticoids (prednisone equivalent <10 mg/day) do not adversely impact vaccine response. 5
• The vaccine can be safely administered to patients on glucocorticoids, with only mild disease flares (4-17%) reported and no serious adverse events. 5

Patients on JAK Inhibitors (e.g., Tofacitinib):

• Complete the full 2-dose series before starting tofacitinib whenever possible, as JAK inhibitors significantly increase herpes zoster risk through impaired interferon-γ signaling. 5
• If urgent initiation is required, give the first dose, start tofacitinib 2-3 weeks later, and complete the second dose 1-2 months after the first. 5

Hematopoietic Stem Cell Transplant Recipients:

• Administer RZV 50-70 days post-transplantation. 5

Patients with Prior Herpes Zoster:

• Vaccinate regardless of prior herpes zoster history, waiting at least 2 months after acute symptoms resolve. 5, 8
• Prior infection does not provide reliable protection against recurrence. 5

Patients Previously Vaccinated with Zostavax:

• Administer the full 2-dose Shingrix series at least 2 months after the last Zostavax dose, as Zostavax efficacy declines to only 14.1% by year 10. 5, 8

VZV-Seronegative Patients:

• If confirmed VZV-seronegative by serology, administer varicella vaccine (2 doses separated by 4 weeks) instead of or before shingles vaccine. 5
• However, 88-91% of adults have VZV antibodies even without recalled chickenpox, so most patients without chickenpox history are actually seropositive. 5

Vaccine Safety Profile

• Common side effects include injection-site reactions (9.5% grade 3) and systemic symptoms (11.4%), which are transient and mild-to-moderate, resolving within 4 days. 5, 8
• No serious safety concerns or increased mortality have been identified in large trials. 5, 8
• Mild disease flares can occur in autoimmune disease patients but without serious adverse events. 5

Antiviral Prophylaxis

For patients at extremely high risk or unable to receive vaccination, antiviral prophylaxis with valacyclovir or acyclovir may be considered, though this is not a substitute for vaccination. 10, 11

• Valacyclovir and acyclovir have demonstrated efficacy in preventing VZV reactivation in clinical trials. 10
• This approach is typically reserved for specific high-risk scenarios (e.g., immediately post-transplant) and is not standard practice for routine prevention. 6

Infection Control Measures

• Routine hand hygiene and appropriate use of isolation precautions and personal protective equipment are essential in healthcare settings. 6
• These measures are particularly important for immunocompromised patients who may have atypical presentations. 6

Critical Clinical Pitfalls to Avoid

• Never administer live-attenuated Zostavax to immunocompromised patients—only Shingrix is safe and appropriate. 5, 8
• Do not delay vaccination to conduct varicella serology in adults aged 50 and older—most have been exposed even without clinical disease. 5
• Do not assume absence of recalled chickenpox means VZV-seronegative status—88-91% of adults have been exposed. 5
• Do not unnecessarily delay vaccination in patients already on immunosuppressive therapy—vaccinate immediately as the vaccine remains effective. 5
• Do not confuse varicella (chickenpox) vaccination with herpes zoster vaccination—these are different vaccines for different populations. 5