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which spread is then via peripheral sensory nerves back to other, usually adjacent, skin and
mucosal sites.[461]
Thus, vesicular HSV or VZV lesions may later appear or recur away from the initial site
of involvement. After an initial host response in which both cell-mediated and humoral
mechanisms take part, the infection usually becomes latent, with HSV or VZV present but not
actively replicating within ganglia. It is unclear just how reactivation of HSV, or VZV as VZV,
occurs but lack of cell-mediated immunity in immunocompromised patients may be
implicated.[461]
The typical patient with HSV or VZV has a grouped vesicular skin eruption that ruptures,
crusts, and heals in seven to ten days. Infection may be associated with a history of severe pain,
often persisting for months after the skin lesions resolve. Scarring also occurs. Reactivation of
VSV as shingles may often occur as an early manifestation of immune impairment with HIV
infection as the CD4 cell count diminishes below 500/µL, though development of VZV does not
appear to be associated with duration of HIV infection, nor does the presence of VZV predict
faster progression of AIDS.[463] The incidence of VZV may increase as a consequence of
immune restoration disease (IRD) in the months following the start of successful antiretroviral
therapy (ART).[285]
In persons with HIV infection, as with immunocompetent individuals, recurrent lesions
of HSV predominantly involve skin and mucus membranes, while the lesions of VZV are
typically limited to skin. Internal organ involvement has been reported less frequently, and
disseminated infections are uncommon, but the clinical course of recurrence is similar to that
seen in other immunocompromised patients or even immunocompetent persons. The upper
gastrointestinal tract including tongue, oropharynx, and esophagus may occasionally have
herpetic lesions, and the central nervous system is less commonly involved (Table 5). Herpetic
mucocutaneous lesions of immunocompromised patients, including those with AIDS, have been
reported to be more extensive, more severe, and longer-lasting, with more ulceration, necrosis,
and pain than in immunocompetent patients.[457,461,464]
In addition to typical VZV findings, the patient with HIV infection can have chronic
VZV, particularly when CD4 lymphocyte counts are low. The clinical appearance of the
chronic, verrucous VZV lesions is that of single or multiple pox-like or wart-like hyperkeratotic
and well-demarcated lesions, which vary from 4 mm to 10 cm in diameter at any skin site.
Lesions often persist from weeks to months, including extension or regression without healing.
Healing may occur within 2 to 3 weeks following therapy, often with residual scarring. Chronic
VZV may follow initial varicella infection, often in children, or it may develop directly from
shingles, or may arise without apparent classic lesions from direct hematogenous dissemination
from reactivated virus in dorsal root ganglia. Treatment with acyclovir may be effective at first,
but thymidine kinase-dependent drug resistance can develop. Then a DNA polymerase inhibitor
such as foscarnet may be employed. Cidofovir has been used when resistance occurs.[465]
Pathologic findings with chronic VZV include hyperkeratosis and parakeratosis of the
verrucous lesions with papillomatous to pseudoepitheliomatous epidermal hyperplasia. Cowdry
type A inclusions and keratinocyte necrosis can be present, as well as swollen keratinocytes
without cytolysis. Though there can be an underlying dermal inflammatory infiltrates of
lymphocytes and/or neutrophils, it is usually minimal or absent.[465]
Although cytologic or histologic diagnosis is simple and cost-effective, viral culture
remains the most sensitive clinical method for HSV or VZV diagnosis; methods for antigen
detection are less sensitive. Culture sensitivity is higher when the herpetic vesicular lesions first