Chronic active varicella zoster virus infection

This case report illustrates previously undescribed features of chronic active varicella zoster virus (VZV) infection, including a 4-month delay between the onset of zoster and zoster sine herpete, involvement of 9 dermatomes on progression of zoster to zoster sine herpete, and the presence of both VZV DNA and anti-VZV immunoglobulin G (IgG) in the CSF.

Case report.

In July 2010, a 58-year-old insulin-dependent diabetic woman developed right-sided T3–4 distribution zoster treated with valacyclovir, 1 g TID for 10 days. Pain persisted. Two months later, she was retreated for 10 days without pain relief. In November 2010, she experienced left-sided T5–8 radicular pain. Neurologic examination revealed left-sided T5–10 hypalgesia. Pain continued. In February 2011, thoracic MRI was normal. She declined electrodiagnostic studies. In April 2011, persistent left T5–8 pain expanded rostral to T2 and caudal to T10. CSF was acellular; protein 123 mg%; no oligoclonal bands. Virologic analysis revealed 5,600 copies of VZV DNA per mL of CSF, but not herpes simplex virus (HSV) DNA or anti-HSV antibody. Anti-VZV IgG antibody was found in CSF, and serum/CSF ratio of anti-VZV IgG antibody was markedly reduced (7.6) compared to ratios for albumin (56) and total IgG (92), indicating intrathecal synthesis of anti-VZV IgG. No VZV DNA was found in blood mononuclear cells or saliva on 4 consecutive days. In May 2011, she was treated with IV acyclovir, 10 mg/kg TID for 3 weeks. Three weeks later, pain decreased “70%–80%.” She was maintained on oral valacyclovir, 1 g TID for 6 more weeks, and continued to improve. In July 2011, because of financial problems, she stopped insulin; 1 month later, blood glucose level was 283 mg% and left-sided pain “increased 50%.” Her diabetes was then treated with metformin and she was restarted on antiviral therapy, with considerable improvement in pain.

Discussion.

Our patient developed classic right-sided T3–4 distribution zoster complicated by postherpetic neuralgia (PHN). Four months after zoster, she developed left-sided pain without rash involving 4 dermatomes (T5–8). Within another 5 months, the left-sided pain spread rostrally to T2 and caudally to T10, indicating involvement of 9 dermatomes. At this time (9 months after zoster), VZV DNA and anti-VZV IgG antibody were found in CSF. Overall, when our patient experienced PHN on the right and extensive zoster sine herpete on the left, virologic analysis revealed active VZV infection.

This unique case illustrates multiple heretofore undescribed and remarkable features of chronic active VZV radiculopathy. First, the interval between zoster and zoster sine herpete is usually only days,¹ in contrast to the development of zoster sine herpete in our patient 3 months after zoster. Second, zoster followed by zoster sine herpete does not progress to involve 9 dermatomes as in our patient. Third, while original cases of zoster sine herpete were verified virologically by detection of VZV DNA² or anti-VZV IgG antibody in CSF,³ our patient had both abundant VZV DNA and anti-VZV IgG antibody in CSF.

It is possible that chronic VZV radiculopathy, multidermatomal pain, and its persistence after oral antiviral treatment were due in part to diabetes, which increases the risk for VZV reactivation. Compared to the well-known decline in VZV-specific cell-mediated immunity (CMI) in healthy individuals with increasing age, diabetic patients stratified by decade have even lower CMI responses to VZV⁴ and are at significantly higher risk for zoster.⁵

Protracted zoster sine herpete in multiple dermatomes distinct from the site of the patient's initial zoster indicates chronic active VZV ganglionitis. Chronic VZV ganglionitis also presents as 1) prolonged pain without rash in individuals with no history of zoster²; 2) prolonged pain (preherpetic neuralgia) before zoster rash; and 3) longstanding radicular pain due to an inflammatory ganglionic mass productively infected with VZV.⁶ The ability of VZV to reactivate from some dermatomes with rash and from other dermatomes without rash is supported by studies with simian varicella virus (SVV), the counterpart of human VZV, in monkeys, where productive SVV virus infection was found in ganglia on the opposite side of the neuraxis 1–4 months after zoster.⁷

Finally, clinical-virologic correlation in our patient, along with resolution of both right-sided PHN and left-sided zoster sine herpete after IV antiviral treatment, strongly suggests that PHN is due to chronic active VZV ganglionitis. Although neither PHN nor zoster sine herpete has been treated effectively with oral antiviral therapy, zoster sine herpete resolved after treatment with IV acyclovir.² If active VZV infection is diagnosed in patients with PHN, IV treatment with acyclovir may be helpful, as it was in our patient.