How Shingles Develops
Shingles develops when the varicella-zoster virus (VZV), which remains dormant in nerve ganglia after an initial chickenpox infection, reactivates due to declining cell-mediated immunity and travels along sensory nerves to cause a characteristic painful, unilateral dermatomal rash. 1
The Pathophysiologic Mechanism
The development of shingles follows a specific sequence:
Primary infection with VZV causes chickenpox, after which the virus becomes latent in dorsal root ganglia or cranial nerve ganglia (particularly trigeminal and geniculate ganglia). 1, 2 This latency period can last decades, during which no virus particles are produced and no obvious neuronal damage occurs. 2
Approximately 95-99% of adults harbor latent VZV capable of reactivation. 1 This includes individuals who received varicella vaccine, as vaccine-strain VZV also establishes latency in ganglia, though their reactivation risk appears lower than after wild-type infection. 1
The critical trigger for shingles is declining VZV-specific cell-mediated immunity, which normally suppresses the latent virus. 1, 3 When this immune surveillance weakens, the virus reactivates within a ganglion and replicates. 4
The reactivated virus spreads along the sensory nerve to the skin dermatome innervated by that specific nerve root, producing the characteristic unilateral vesicular rash. 1, 4 This explains why shingles affects only one side of the body in a band-like distribution.
Risk Factors for Reactivation
Several factors precipitate the decline in cell-mediated immunity:
Advancing age is the most significant risk factor, with incidence rising sharply after age 50 due to natural waning of VZV-specific cellular immunity. 1, 3 Shingles predominantly affects the elderly population. 3
Immunosuppressive conditions substantially increase risk, including HIV infection, malignancies, chemotherapy, and chronic corticosteroid use. 5, 6 Patients with rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, and inflammatory bowel disease have elevated risk with risk ratios ranging from 1.23 to 2.08. 1
Recent evidence identifies COVID-19 as an associated factor in shingles reactivation. 1
Physical stressors such as hard work and emotional stress may contribute to reactivation. 6
Clinical Manifestation Timeline
The disease follows a predictable pattern:
Burning pain typically precedes the rash by 24-72 hours in most cases. 1, 5 This prodromal pain occurs in the affected dermatome before any visible skin changes.
Local edema and erythema appear before the rash develops. 6 The rash then evolves from maculopapular to vesicular lesions, which eventually crust over. 6
Patients remain contagious from 1-2 days before rash onset until all lesions are crusted. 1 The vesicle fluid contains enormous amounts of virus particles and can transmit varicella to susceptible individuals. 6
Common Pitfalls
Do not assume immunity to varicella prevents shingles—immunity protects against reinfection with varicella but does not prevent reactivation of latent virus. 2
Recognize that immunocompromised patients, particularly those with HIV, may present with atypical features including involvement of two or more dermatomes, hemorrhagic lesions, cutaneous dissemination, and visceral involvement. 6
Be aware that zoster sine herpete (pain without rash) can occur and requires laboratory confirmation for diagnosis. 6