Immune deviation and ocular infections with varicella zoster virus.

Since experimental, herpes simplex virus-induced acute retinal necrosis (ARN) develops in mice only if the mice fail to acquire virus-specific delayed hypersensitivity (DH) and despite their production of anti-viral antibodies (i.e. ACAID), I investigated whether a similar situation exists for patients with either varicella zoster virus (VZV)-induced ARN or anterior uveitis caused by VZV. Patients with either acute VZV-induced ARN, anterior uveitis with dermatitis (herpes zoster ophthalmicus, ZO-AU), or anterior uveitis without dermatitis (zoster sine herpete, ZSH-AU) were skin-tested with VZV to evaluate DH. The formal diagnoses of ARN associated with VZV, ZO-AU, and ZSH-AU were established by PCR analysis of the ocular samples and/or by the Goldmann-Witmer coefficient to determine levels of local antibody production. ARN, ZO-AU, and ZSH-AU activity were assessed clinically, and DH skin tests were repeated three 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 antigen. In contrast, subsets of patients with ARN or ZO-AU displayed loss of VZV-specific DH. Patients with the most severe ARN or ZO-AU had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in ARN patients than in normal controls, and the anti-viral titer correlated inversely with the intensity of anti-VZV DH responses. VZV-specific DH responses were restored in patients who recovered from ARN. Patients with ZSH-AU also failed to display VZV-specific DH. The absence of DH reactivity to VZV antigens (i.e. immune deviation) appears to be a concomitant feature of VZV uveitis of high intensity, implying that virus-specific DH may interfere with the emergence of VZV-induced ARN or anterior uveitis.