How Shingles Develops
Shingles develops when the varicella-zoster virus (VZV), which remains dormant in dorsal root ganglia or sensory ganglia of cranial nerves after primary chickenpox infection, reactivates due to declining cell-mediated immunity. 1
The Pathophysiologic Mechanism
Primary Infection and Latency Establishment:
- After initial varicella (chickenpox) infection—typically during childhood—VZV travels along sensory nerve fibers and establishes permanent latency in neuronal ganglia, particularly the dorsal root ganglia and cranial nerve ganglia. 1
- During latency, no virus particles are produced and no obvious neuronal damage occurs; the virus remains dormant but viable within these neurons. 2
- Approximately 95-99% of adults have been infected with VZV and therefore harbor latent virus capable of reactivation. 1
Reactivation Trigger:
- The critical factor is declining cell-mediated immunity to VZV, which normally keeps the latent virus suppressed. 1
- This immune decline occurs naturally with aging, which explains why disease incidence increases markedly beginning at approximately 50 years of age. 1, 3
- Approximately 20-30% of people will develop shingles over their lifetime. 1, 3
Risk Factors That Precipitate Reactivation
Age-Related Immune Decline:
- The most significant risk factor is advancing age, with incidence rising sharply after age 50 due to natural waning of VZV-specific cellular immunity. 1, 4
Immunocompromising Conditions:
- HIV infection, active malignancies, chemotherapy, chronic corticosteroid use, and other immunosuppressive therapies significantly increase reactivation risk. 5, 6
- Patients with conditions like rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, and inflammatory bowel disease have elevated risk (risk ratios ranging from 1.23 to 2.08). 1
- Recent evidence identifies COVID-19 as an associated factor. 1
Other Contributing Factors:
- Physical or emotional stress, hard work, and general debilitation may contribute to immune decline and subsequent reactivation. 6
The Reactivation Process
From Ganglia to Skin:
- When immunity fails to control latent VZV, the virus begins replicating within the affected ganglion. 5, 7
- The reactivated virus then spreads along the sensory nerve to the skin area (dermatome) innervated by that specific nerve root. 1, 7
- This produces the characteristic unilateral, dermatomal vesicular rash with associated pain. 1
Clinical Manifestation Timeline:
- Burning pain typically precedes the rash by several days (24-72 hours in most cases). 3, 5
- The rash evolves from maculopapular lesions to vesicles to pustules, then crusts over 4-7 days. 1
- Patients remain contagious from 1-2 days before rash onset until all lesions are crusted. 1
Important Clinical Caveats
Prior Vaccination Does Not Prevent Reactivation:
- Individuals who received varicella vaccine (rather than natural infection) still harbor latent vaccine-strain VZV in their ganglia and remain at risk for shingles, though this risk appears lower than after wild-type infection. 1
Recurrence Is Possible:
- While uncommon in immunocompetent hosts, shingles can recur, particularly in immunocompromised patients including those with HIV infection. 6
Contagiousness:
- The vesicular fluid contains enormous amounts of infectious VZV particles capable of causing chickenpox (not shingles) in susceptible, non-immune individuals. 6