A relationship between varicella-zoster virus-specific delayed hypersensitivity and varicella-zoster virus-induced...

We recently reported that acute retinal necrosis in humans develops in a setting where delayed hypersensitivity (DH) to the varicella-zoster virus (VZV) antigen was absent, implying that virus-specific DH mitigates against acute retinal necrosis.

To determine whether a similar correlation exists for patients with anterior uveitis caused by VZV.

Using VZV and purified protein derivative (PPD) antigens to evaluate DH, we skin tested patients with acute, VZV-induced anterior uveitis (herpes zoster ophthalmicus [ZO-AU]) (n = 12), those with uveitis caused by VZV in the absence of dermatitis (zoster sine herpete [ZSH-AU]) (n = 3), and age-matched patients whose ophthalmic herpes zoster was unassociated with uveitis as controls (n = 7). Varicella-zoster virus-induced anterior uveitis was diagnosed by polymerase chain reaction methods and serum antibody titration. Serum samples were collected and analyzed for anti-VZV antibody titers. Anterior uveitis activity was assessed clinically. Delayed hypersensitivity skin tests were repeated in patients with zoster sine herpete 3 months after onset, when ocular recovery had taken place.

All patients with VZV-induced skin disease alone (control group) displayed intense DH when tested with VZV and PPD antigens. By contrast, only 4 (33%) of 12 patients with ZO-AU had a positive DH to VZV, whereas 11 (91.6%) of these patients displayed positive PPD skin reactions. The clinical intensity of anterior uveitis correlated negatively with VZV DH responses (P<.05). Serum anti-VZV and anti-herpes simplex virus antibody titers were comparable in DH-positive VZV cases and in DH-negative patients with uveitis. Patients with uveitis and ZSH-AU also displayed absent VZV-specific DH, although their PPD responses were normal.

Varicella-zoster virus-specific DH, PPD-specific DH, VZV-specific antibody titration, and intraocular pressure in patients with ZO-AU.

Absence (or loss) of DH reactivity to VZV antigens seems to be a concomitant feature of VZV uveitis of high intensity, implying that virus-specific DH may interfere with the emergence of VZV-induced anterior uveitis, as it does for acute retinal necrosis.

In a clinical setting, absence of virus-specific DH to anterior uveitis caused by VZV may not only reveal a possible pathogenic mechanism, but a negative DH response may prove useful in diagnosing ZSH-AU in the acute stage.