Varicella-zoster virus (VZV) remains latent in cranial and dorsal root ganglia with the potential for reactivation as shingles (zoster). Neurologic complications can occur with VZV infection, especially in the immunocompromised, and usually in association with a vesicular exanthem. We report the case of a previously healthy immunocompetent 14-year-old boy with acute aseptic meningitis without exanthem as a result of reactivated VZV infection.
A 14-year-old boy was admitted to hospital with a 1-week history of severe frontal headache and a 3-day history of vomiting and photophobia. The headaches were debilitating, persistent, thumping in character, and relieved by analgesia and vomiting. There was no history of pallor or visual disturbances.
The patient had a 5-year history of migraine headaches. The headaches on this occasion were more severe, and the vomiting more persistent. He had an episode of varicella at the age of six, but no history of zoster.
His medical history was otherwise unremarkable. He was not on any regular medications. There was a family history of migraine.
On examination, the patient was alert, oriented, and interactive. His vital signs were normal. He was apyrexial. He had no skin lesions. There was no neck stiffness or meningism. His pupillary reflexes were normal. Fundoscopy was normal. Tone, power, coordination, and deep tendon reflexes were normal in all 4 limbs. He had no sensory deficit or disturbance.
Blood tests revealed normal renal, liver and bone biochemistry, normal C-reactive protein, and a white cell count and differential as follows: leukocyte count 5.1 × 103 per mm3 (61% neutrophils, 28% lymphocytes, 9% monocytes, and 1% eosinophils). Chest roentgenogram and computed tomography (CT) of the brain performed at presentation were normal.
Cerebrospinal fluid (CSF) samples were taken at presentation. The CSF cell count was 285 white cells and 15 red cells/mm3 with a protein of 158 mg/dL and glucose of 1.9 mmol/L (blood glucose of 5.2 mmol/L). No bacteria were seen on CSF Gram stain, and CSF cultures were negative. A CSF sample was sent to the National Virus Reference Laboratory, University College Dublin. CSF polymerase chain reactions (PCR) for herpes simplex virus I and II, enterovirus and cytomegalovirus were negative. VZV DNA was detected in the CSF sample by PCR. A second sample of CSF, taken 6 days later, had 186 white cells (99% mononuclear cells, 1% polymorphs) and 3 red cells/mm3 with a protein of 68 mg/dL, and glucose of 2.4 mmol/L. VZV DNA was again detected by PCR. An MR brain scan performed on day 5 was normal. Serum VZV-antibody titers were examined by time resolved fluorescent immunoassay and results were as follows: IgG 1763 mIU/mL with high IgG avidity, IgM negative (acute), and IgG 2400 mIU/mL with high IgG avidity, IgM negative (convalescent), consistent with established VZV infection. Serology for human immunodeficiency virus (HIV) was nonreactive, and serum immunoglobulin values were within normal limits. The patient was treated with IV aciclovir for 10 days, followed by oral valaciclovir for 4 days. His symptoms resolved within 3 days of presentation and he was discharged home. He has had no recurrence of headache, but at 6 month follow-up had persistent fatigue.
PCR is an inexpensive, rapid, and highly sensitive method of detecting herpes viruses, and its development has made diagnosis of neurologic disease related to VZV much easier. We now know that reactivated VZV can cause a broad spectrum of neurologic disease.1,2 We also know that VZV-related neurologic disease can occur without the classic herpes zoster exanthem. Evidence for this initially came indirectly from serum antibody studies or detection of VZV-specific antibodies in CSF.3,4 Subsequently, Echevarria et al reported 6 cases of VZV-related aseptic meningitis without rash confirmed by PCR.5 These reports changed our understanding of reactivated VZV-related neurologic disease, because they implied that virus could travel directly from the spinal ganglia, where they had lain dormant, to the central nervous system and cause disease. Although such cases have been reported, they are still relatively uncommon, especially in the immunocompetent pediatric population. Jhaveri et al described a case of aseptic meningitis in a healthy 12-year-old boy,6 and Chiappini et al described a case of encephalitis resulting from reactivated VZV in an otherwise healthy 2-year-old child,7 both without viral exanthem. Both of these children had a history of varicella below the age of 2. Varicella in infancy and early childhood is a risk factor for reactivated-VZV related neurologic complications. Our patient had primary varicella at the age of 6, considerably later than the 2 cases mentioned above.
We believe our case emphasizes the importance of considering reactivated VZV as a potential cause of acute aseptic meningitis in immunocompetent pediatric patients, even without a history of recent cutaneous zoster or varicella in infancy. Whether such cases represent self-limiting episodes of viral reactivation,8 or always demand treatment with antiviral medications remains unclear.
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