Herpes Zoster Etiology
Herpes zoster is caused by reactivation of varicella-zoster virus (VZV) that remains latent in dorsal root ganglia following primary varicella (chickenpox) infection. 1, 2
Pathophysiology
After primary VZV infection (chickenpox), the virus establishes lifelong latency in sensory nerve ganglia. 1 The virus can subsequently reactivate to cause herpes zoster when cell-mediated immunity declines. 1, 3
Key mechanisms controlling VZV latency are not fully understood, but reactivation occurs when VZV-specific cell-mediated immunity wanes. 1, 3
Risk Factors for Reactivation in Autoimmune Disease Patients
Patients with autoimmune diseases like rheumatoid arthritis face substantially elevated risk for herpes zoster through multiple mechanisms:
Disease-Related Risk
- The autoimmune disease itself confers increased risk independent of treatment. Inflammatory bowel disease patients show relative risk of 1.74 for Crohn's disease and 1.40 for ulcerative colitis. 1
- Decreased cell-mediated immunity from the underlying autoimmune condition predisposes to VZV reactivation. 1
Immunosuppressive Therapy-Related Risk
- Corticosteroids significantly increase herpes zoster risk (RR 1.78-1.99 depending on the condition). 1
- Anti-TNF agents confer RR of 2.29 for herpes zoster. 1
- Thiopurines (azathioprine, 6-mercaptopurine) increase frequency and severity of herpes zoster reactivation. 1
- Methotrexate increases risk of VZV reactivation. 1
- The risk increases further when multiple immunosuppressive agents are combined. 1
Clinical Implications for Immunocompromised Patients
Immunocompromised patients experience more severe and prolonged disease compared to immunocompetent hosts. 1, 4
Key differences include:
- Lesions continue to develop for 7-14 days (versus 4-6 days in immunocompetent patients). 5
- Higher risk of disseminated disease involving multiple dermatomes or visceral organs. 1
- Potential for chronic ulcerations with persistent viral replication without adequate treatment. 4, 5
- Increased risk of life-threatening complications including pneumonia, hepatitis, encephalitis, and hemorrhagic disorders. 1
Prevention Considerations
Recombinant zoster vaccine (Shingrix) is the preferred vaccine for patients with autoimmune diseases, including those on immunosuppressive therapy. 1 This non-live vaccine is safe in immunocompromised patients and demonstrates superior efficacy compared to the live-attenuated vaccine. 1, 6
The live-attenuated vaccine (Zostavax) is generally contraindicated in immunocompromised patients due to risk of vaccine-strain VZV infection, though it may be considered in patients on low-dose immunosuppression (methotrexate <0.4 mg/kg/week, azathioprine <3.0 mg/kg/day, prednisone <20 mg/day). 1