The pathologic changes in VZV infection consist of one or more of the following: (1) an inflammatory reaction in several unilateral adjacent sensory ganglia of the spinal or cranial nerves, frequently of such intensity as to cause necrosis of all or part of the ganglion, with or without hemorrhage; (2) an inflammatory reaction in the spinal roots and peripheral nerve contiguous with the involved ganglia; (3) a less-common poliomyelitis that closely resembles acute anterior poliomyelitis but is readily distinguished by its unilaterality, segmental localization, and greater involvement of the dorsal horn, root, and ganglion, sometimes with necrosis; and (4) a relatively mild leptomeningitis, largely limited to the involved spinal or cranial segments and nerve roots. These pathologic changes are the substrate of the neuralgic pains, the pleocytosis, and the local palsies that may attend and follow the VZV infection. There may also be a delayed cerebral vasculitis (see Zoster Angiitis).
As to pathogenesis, herpes zoster represents a spontaneous reactivation of VZV infection, which becomes latent in the neurons of sensory ganglia following a primary infection with chickenpox (Hope-Simpson). This mechanism is consistent with the differences in the clinical manifestations of chickenpox and herpes zoster, even though the same virus causes both. Chickenpox is highly contagious by respiratory aerosol, has a well-marked seasonal incidence (winter and spring), and tends to occur in epidemics. Zoster, on the other hand, is not communicable (except to a person who has not had chickenpox), occurs sporadically throughout the year, and shows no increase in incidence during epidemics of chickenpox. In patients with zoster, there is practically always a past history of chickenpox. Such a history may be lacking in rare instances of herpes zoster in infants, but in these cases, there has usually been prenatal maternal contact with VZV.
VZV DNA is localized primarily in trigeminal and thoracic ganglion cells, corresponding to the dermatomes in which chickenpox lesions are maximal and that are most commonly involved by VZV (Mahalingam et al). The supposition is that the virus makes its way from the cutaneous vesicles of chickenpox along the sensory nerves to the ganglion, where it remains latent until activated, at which time it progresses down the axon to the skin. Multiplication of the virus in epidermal cells causes swelling, vacuolization, and lysis of cell boundaries, leading to the formation of vesicles and so-called Lipschütz inclusion bodies. Alternatively, the ganglia could be infected during the viremia of chickenpox, but then one would have to explain why only one or a few sensory ganglia become infected. Reactivation of virus is attributed to waning immunity, which would explain the increasing incidence of zoster with aging and with lymphomas, administration of immunosuppressive drugs, HIV, and after radiation therapy. Increasingly, monoclonal antibodies and other immunosuppressive drugs have been associated with the reemergence of zoster, mostly as dermatomal shingles but also, in extreme cases, as a generalized systemic illness or eruption.
The subject of pathogenesis of herpes zoster has been reviewed by Gilden and colleagues (2000) and in the monograph by Rentier, who describes the molecular and immune investigations pertaining to VZV.