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Viral Infections
The Legend of Recurrent Zoster, and Other Tales of Varicella Zoster Virus
a report by
Andy J Chien, MD, PhD and Andrea A Kalus, MD
Division of Dermatology, University of Washington
In 1767, the renowned physician William Heberden went before the likely recurrent herpes simplex virus (HSV) or zosteriform simplex, despite
College of Physicians in London to propose that varicella (chickenpox) the fact that reports of misdiagnosed recurrent zoster actually
and variola (smallpox) represented two completely unrelated entities, an outnumber cases of laboratory-confirmed recurrent zoster in the medical
assertion that was echoed a quarter of a century later by none other than literature.
4,5
In fact, there are more cases of recurrent varicella in
the great Sir William Osler. Around the same time, the Hungarian immunocompetent children than there are cases of confirmed recurrent
pediatrician James Von Bokay reported on children who developed herpes zoster in immunocompetent patients.
6
chickenpox after coming into contact with an individual who had herpes
zoster, prompting him to suggest that herpes zoster and chickenpox The distinction is not trivial. Besides the differences in the dosing of
could represent different presentations of the same infectious agent. antiviral medications for VZV compared with those for HSV, there are
However, it was not until 1952 that Weller and Stoddard isolated implications for transmissibility that affect patients, healthcare workers,
varicella zoster virus (VZV) as the etiological agent in herpes zoster and close contacts. After all, reactivated zoster poses a risk primarily to
lesions.
1
Over half a century later, questions still remain regarding the individuals who are immunocompromised or who have not had
processes governing the latency and reactivation of VZV. chickenpox. On the other hand, non-venereal transmission of HSV has
been well documented, including entities such as herpes gladiatorum—
Recurrent Zoster—Fact or Fiction? seen among wrestlers or others with close contact—and eczema
We recently reviewed the literature on recurrent herpes zoster in herpeticum—commonly seen in dermatology among children with severe
immunocompetent individuals, concluding that true recurrent zoster in atopic dermatitis flares.
7,8
In addition, HSV has been isolated from a
this population is a rare event.
2
Unexpectedly, this conclusion was met variety of inanimate objects, ranging from hot tubs in spa facilities to
with tremendous skepticism by expert peer reviewers in dermatology, common household objects made of plastic.
9
internal medicine, and infectious disease. One reviewer summed up the
opinions of the group best by stating: “It is my clinical experience that While increased risk of recurrent herpes zoster has been recognized in
recurrent zoster is not so rare.” This assertion is totally unsupported by the setting of HIV infection, there are no reports of increased recurrence
the literature, which includes a recent large study of 38,546 rates in other immunosuppressed populations such as patients with
immunocompetent patients that suggested the rate of recurrent zoster hematological malignancies or patients on immunosuppressive
was no higher than three in 1,308 (0.23%).
3
Nevertheless, many medication regimens, both of which groups are at increased risk for a
clinicians continue to diagnose patients with recurrent zoster that is most first episode of herpes zoster. While cell-mediated immunity clearly plays
a role in reactivation, the exact mechanisms underlying both immune
evasion by VZV and the role of the immune system in preventing
Andy J Chien, MD, PhD, is an Assistant Professor in the Division
persistent reactivation remain unresolved. While 90% of individuals have
of Dermatology at the University of Washington. His primary
VZV in their trigeminal ganglion upon post-mortem analysis using
research focus is signal transduction pathways that regulate
oncogenesis and metastasis.
polymerase chain reaction (PCR)-based methods of detection, a much
smaller percentage of patients will actually develop trigeminal-based
E:
andchien@u.washington.edu
herpes zoster in their lifetime.
11
One might ask why it is uncommon for VZV to repeatedly reactivate
while the related neurotrophic HSV reactivates quite commonly.
Andrea A Kalus, MD, is an Assistant Professor in the Division of
Dermatology at the University of Washington. She is board-
Although both viruses achieve latency in sensory ganglia for the lifetime
certified in both dermatology and internal medicine, and her of an affected individual, several studies have demonstrated that VZV
current research involves the role of antimicrobial peptides in
achieves latency in both the neurons and satellite cells of sensory ganglia,
skin disease and keratinocyte biology. Together, Drs Kalus and
Chien supervise the Residency Continuity Clinic at the University
while HSV latency appears to be limited to neurons.
12,13
This observation
of Washington, where they share an interest in complex medical may account for the fact that VZV reactivation can be quite broad, with
dermatology cases.
skin lesions often extending beyond one dermatome, while HSV
recurrences are often more limited in their distribution. Neuronal cells do
not normally express major histocompatibility complex (MHC) class I in
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