Classic zoster sine herpete (ZSH) is defined clinically as dermatomal distribution pain without rash. ZSH was designated as a nosologic entity based on virologic confirmation in 3 men over age 60 with chronic thoracic-distribution radicular pain, with amplifiable varicella zoster virus (VZV) DNA found in CSF of the first 2 patients1 and in blood mononuclear cells (MNCs) in the third patient.2 Herein, we describe a patient who developed radicular pain without rash in the same dermatome as his initial cervical-distribution zoster episode, but with a remarkably prolonged interval between episodes, and in whom ZSH was virologically confirmed by the detection of anti-VZV immunoglobulin G (IgG) antibody in CSF with serum/CSF ratios indicative of intrathecal antibody synthesis.
Case report.
In 2008, a 77-year-old man developed right C8-distribution zoster; he was not treated with an antiviral agent or steroids and his rash and pain resolved completely. One year later, he developed colon cancer and was treated every other week for 7 months with a protocol using leucovorin, 5-fluorouracil, oxaliplatin, and folinic acid.3 In November 2009, right C7–8-distribution pain recurred, but in the absence of rash. In December 2009, he developed a painless right foot drop. In February 2010, neurologic examination revealed C7–8 thigmesthesia and allodynia and an incidental right peroneal palsy. All deep tendon reflexes were reduced or absent. Cervical MRI revealed degenerative changes at C5–6 and C6–7 without root compression. The CSF was acellular; cytology was negative, and CSF protein was 87 mg%. A presumptive diagnosis of ZSH was made, and he was treated with valacyclovir, 1 g 3 times daily for 14 days, and pregabalin, 150 mg at night. A few days after treatment, he experienced a dramatic reduction in pain, and 2 months later, was pain-free. Virologic studies of the CSF and serum obtained before antiviral treatment revealed no amplifiable VZV or herpes simplex virus (HSV) DNA and no anti-HSV IgG antibody. In contrast, anti-VZV IgG antibody was present, and the serum/CSF ratio of anti-VZV IgG antibody was markedly reduced (4.9) compared to ratios for albumin (70) and total IgG (150), indicative of intrathecal synthesis of anti-VZV IgG.
Discussion.
Analysis of our patient revealed 2 remarkable features. First, although the development of radicular pain without rash in the same dermatome as earlier zoster in our patient is much like the earlier description of radicular pain without rash days after zoster in a different dermatome,4 the prolonged interval of 18 months from zoster to later-onset ZSH is unique. Second, intrathecal synthesis of anti-VZV IgG antibody in CSF provided virologic proof of zoster sine herpete; in fact, unlike the other 3 patients with ZSH in whom PCR revealed VZV DNA in CSF1 or blood MNCs,2 our patient's CSF was negative for VZV DNA.
Importantly, intrathecal synthesis of anti-VZV IgG antibody has been shown to be a superior parameter as compared to detection of VZV DNA in CSF in diagnosing VZV vasculopathy,5 and VZV myelopathy in the absence of rash in patients whose CSF did not contain VZV DNA.6,7 Nevertheless, the comparative diagnostic value of these tests awaits virologic analysis in additional cases of ZSH. Until then, CSF should be examined for both VZV DNA and anti-VZV IgG antibody in patients with prolonged radicular pain without rash to verify the diagnosis of zoster sine herpete.
ACKNOWLEDGMENT
The authors thank Marina Hoffman for editorial assistance and Cathy Allen for word processing and formatting the final manuscript.
Footnotes
Disclosure: Dr. Blumenthal serves on a scientific advisory board for Schering-Plough Corp.; has received funding for travel from Roche and Schering-Plough; and has served on the speakers' bureau for Schering-Plough. Dr. Shacham-Shmueli, Dr. Bokstein, and Dr. Schmid report no disclosures. Dr. Cohrs serves on the editorial advisory board for the Archives of Clinical Microbiology and receives research support from the NIH. Dr. Nagel receives research support from the NIH. Dr. Mahalingam serves as an Associate Editor for the Journal of Neurovirology and receives research support from the NIH. Dr. Gilden serves as Senior Associate Editor for the Journal of Neurovirology and on the editorial boards of In Vivo, the Journal of Virology, Scientific American Medicine, Virus Genes, and Neurology®, and receives research support from the NIH.
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
Editorial, page 416
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