title: A relationship between varicella-zoster virus-specific delayed hypersensitivity and varicella-zoster virus-induced anterior uveitis.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tate-machi, Hachioji-city, Tokyo, 193-8639, Japan. tkezuka@tokyo-med.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kezuka
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Minoda
authors.forename: Masaru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Keino
authors.forename: J Wayne
authors.initials: JW
authors.lastname: Streilein
authors.forename: Masahiko
authors.initials: M
authors.lastname: Usui
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D001082:Aqueous Humor / Q000276:immunology; D005260:Female; D006563:Herpes Zoster Ophthalmicus / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012882:Skin Tests; D014606:Uveitis, Anterior / Q000276:immunology* / Q000821:virology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral