Pathophysiology of Herpes Zoster Cicatricial Lesions
Herpes zoster causes cicatricial (scarring) lesions through a sequential process of viral reactivation, neuronal spread, direct cytopathic effects on skin cells, and subsequent inflammatory tissue destruction that progresses from vesicles to pustules to ulceration, ultimately healing with scar formation.
Viral Reactivation and Neural Spread
The pathophysiologic cascade begins when varicella-zoster virus (VZV) reactivates from its latent state in the dorsal root ganglia or sensory ganglia of cranial nerves, typically when cellular immune response fails to control viral replication 1.
VZV spreads from the ganglia to the skin primarily through myelinated nerves, which predominantly terminate around the isthmus of hair follicles 2. Immunohistochemical studies demonstrate that:
- The immediate early protein IE63 (encoded by ORF 63) initially appears in nuclei of follicular epithelial cells and basal/parabasal epidermal cells 2
- Hair follicle involvement occurs with high incidence in early lesions, with viral localization concentrated at the follicular isthmus 2
- VZV infects both permissive cells (capable of viral replication) and non-permissive cells in the affected dermatome 2
Sequential Tissue Destruction
The characteristic dermatomal lesions progress through distinct histopathologic stages that lead to scarring 1, 3:
Early Phase (Days 1-4)
- Erythematous macules rapidly evolve to papules then vesicles 1, 3
- Lesions continue to erupt for 4-6 days in immunocompetent hosts 3
- IE63 protein spreads from nuclei to cytoplasm of infected cells during their degeneration 2
Intermediate Phase (Days 4-7)
- Thin-walled vesicles progress to pustules 1
- Lesions frequently coalesce, particularly in immunocompromised patients 1
- Median time to full crusting is approximately 5-7 days 4, 5
Late Phase and Cicatrization
- Pustules evolve into ulcers, which represent the critical stage for scar formation 1
- In immunocompromised hosts, chronic poorly healing ulcers develop with persistent viral replication 1, 3
- Secondary bacterial and fungal superinfections can occur, exacerbating tissue destruction and scarring potential 1, 3
Factors Increasing Cicatricial Risk
Immunocompromised patients face substantially higher risk of severe scarring due to:
- Development of chronic ulcerations with persistent viral replication 1, 3
- Loss of the vesicular component, making lesions appear as chronic ulcers from onset 1
- Higher rates of lesion coalescence and deeper tissue involvement 1
- Increased susceptibility to secondary infections that worsen tissue damage 1, 3
Clinical Implications
The total disease duration in immunocompetent individuals is approximately 2 weeks 3, but delayed healing significantly increases scarring risk. Early antiviral therapy (within 48-72 hours of rash onset) reduces the duration of ulceration and crusting phases, thereby minimizing cicatricial outcomes 4, 5.
Common Pitfall
Clinicians may underestimate scarring risk in patients presenting with atypical lesions that lack the characteristic vesicular appearance 3. These presentations still undergo the same destructive tissue phases and require prompt antiviral intervention to prevent extensive cicatrization.