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A Relationship Between Varicella-Zoster Virus–Specific Delayed Hypersensitivity and Varicella-Zoster Virus–Induced Anterior Uveitis
Takeshi Kezuka, MD, PhD;
Jun-ichi Sakai, MD, PhD;
Hiroshi Minoda, MD, PhD;
Masaru Takeuchi, MD, PhD;
Hiroshi Keino, MD, PhD;
J. Wayne Streilein, MD;
Masahiko Usui, MD, PhD
Arch Ophthalmol. 2002;120:1183-1188.
Background 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.
Objective To determine whether a similar correlation exists for patients with
anterior uveitis caused by VZV.
Design 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.
Results 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.
Main Outcome Measures Varicella-zoster virus–specific DH, PPD-specific DH, VZV-specific
antibody titration, and intraocular pressure in patients with ZO-AU.
Conclusions 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.
Clinical Relevance 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.
From the Department of Ophthalmology at Hachioji Medical Center (Dr
Kezuka), and the Department of Ophthalmology at Tokyo Medical University (Drs
Sakai, Minoda, Takeuchi, Keino, and Usui), Tokyo, Japan; and Schepens Eye
Research Institute, Department of Ophthalmology, Harvard Medical School, Boston,
Mass (Dr Streilein).
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