INTRODUCTION: In Part I we presented background on the involvement of varicella zoster virus (VZV) with the enteric nervous system (ENS). That included evidence that reactivation of VZV within the ENS can infect gastrointestinal (GI) targets and cause enteric zoster.

DISCUSSION: Zhou et al.1, present a review detailing the involvement of VZV with the enteric nervous system. The reactivation of VZV with no apparent shingles on the skin surface is called zoster sine herpete (ZSH-Lewis2). ZSH is one of the atypical clinical manifestations of herpes zoster (HZ), which stems from infection and reactivation of (VZV) in the cranial nerve, spinal nerve, viscera, or autonomic nerve. In the US, there are almost one million cases of HZ each year. However, ZSH is likely to be missed or misdiagnosed, and patients may not receive timely antiviral treatment. Even with the high case rates of ZH, there is presently little epidemic data regarding ZSH. Considering that more than 95% of young adults in North American and Europe are positive for VZV, the incidence of both HZ and ZSH is expected to increase as the population ages. And in the case of ZSH, it is likely that this type of reactivation will continue to be under-reported and underrated. In 1958, Lewis2, proposed several observations pointing towards ZSH, based on the type and locations of specific pains.  The pain can be a deep boring/twisting pain arising in muscles, joints, etc., which is called “sclerotome pain”; or a superficial, burning pain in or near the called “dermatomal pain”. The pain from ZSH has been reported to be more serious, than the pain associated with HZ. Unexplained abdominal pain may be related to ZSH because salivary VZV DNA was detected in 6/11 patients of this type, 11/16 patients with zoster or varicella, and 2/2 ZSH patients. However, healthy controls (n=20) and patients with unrelated gastrointestinal disorders (n=8) were all negative for VZV DNA detection (Gershon et al3). These results indicate that ZSH may be the reason for the abdominal pain. Patients with mucosal lesions in the larynx, with sore throat, dysphagia, and hoarseness were VZV DNA positive after detecting exudates from the pharyngeal mucosal lesions. Patients in these studies all responded to, and benefited from, herpes virus antiviral therapy. Studies indicate that at the beginning of ZSH, detection of VZV DNA is more sensitive than anti-VZV antibodies, which show up later in the ZSH reactivation (Furuta et al4).

CONCLUSION: ZSH is a special form of VZV reactivation which often leads to misdiagnosis due to the lack of typical clinical manifestations. ZSH should be considered in patients with unilateral, single-root neuralgia and diagnosed with VZV DNA and/or anti-VZV IgG/IgM. Accurate diagnosis methods, timely antiviral therapy, and more ZSH related studies and guidelines will be beneficial for ZSH diagnosis and treatment.


  1. Zhou, J., J. Li, L. Ma, and S. Cao. (2020). Zoster sine herpete: a review. Korean J Pain 33(3):208-215.
  2. Lewis, GW. (1958). Zoster sine herpete. Br. Med J 2(5093):418-21.
  3. Gershon, A.A., J. Chen, and M.D. Gershon. (2015). Use of saliva to identify varicella zoster virus infection of the gut. Clin Infect Dis 61(4):536-44.
  4. Furuta Y., S. Fukuda, S. Suzuki, T. Takasu, Y. Inuyama, and K. Nagashima. (1997). Detection of varicella-zoster virus DNA in patients with acute peripheral facial palsy by the polymerase chain reaction, and it’s use for early diagnosis of zoster sine herpete. J Med Virol 52:316-9.<316::AID-JMV13>3.0.CO;2-G

MKTG 1071  Rev A   CO-336