Hospital Onset Varicella Central Nervous System Vasculitis in a Patient with HIV Infection

Case

A 35-year-old HIV-infected man with a CD4 count of 70 cells/mL³ and antiretroviral therapy (ART) naive was hospitalized for leg cellulitis, confusion, and grandiose delusions. An admission brain magnetic resonance imaging (MRI) revealed abnormalities consistent with HIV encephalopathy. The patient was treated with antibiotics, antipsychotic medication, and initiated ART with abacavir/lamivudine/dolutegravir. After 1 month, his CD4 increased to 155 cells/mL³ and his viral load decreased 4 logs.

Six weeks after admission while awaiting placement, the patient became confused; an MRI revealed a right corpus callosal hemorrhage with vascular enhancement and abnormal enhancement of the choroidal–retinal layer of the left globe. He subsequently reported blurriness and an ophthalmology examination demonstrated left retinal detachment. A computed tomography angiogram (CTA) of the brain revealed diffuse beaded irregularity of the intracranial arteries consistent with vasculitis (Fig. 1A). Lumbar puncture demonstrated a protein of 110 mg/dL and a WBC count of 5 cells/mcL. Polymerase chain reaction (PCR) tests for cytomegalovirus, herpes simplex virus, and varicella zoster virus (VZV) were negative. A send-out test for cerebrospinal fluid (CSF) VZV IgG returned high at >4,000 index value, which led to a diagnosis of central nervous system (CNS) varicella vasculitis. The patient was treated with a prolonged course of acyclovir, and clinically improved within a few weeks. A follow-up CTA 7 months later showed marked improvement (Fig. 1B).

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FIG. 1.

CT angiography images in a HIV-infected patient with central nervous system varicella vasculitis. (A) At the time of varicella vasculitis diagnosis, note the diffuse segmental arterial irregular beading in branches of the anterior cerebral arteries. (B) Seven months after treatment, significant improvement in arterial beading, but note mild residual nonocclusive irregularity of anterior cerebral arteries. CT, computed tomography. Color images are available online.

This case highlights important clinical points regarding the diagnosis of CNS varicella infection, including the utility of CNS imaging findings, VZV CSF IgG testing, and the importance of including varicella on the differential for hospital onset infections among HIV-infected persons.

The CTA findings in our patient were essential to a diagnosis as it suggested vasculitis was the cause of the callosal hemorrhage, and prompted CSF VZV IgG testing after a negative CSF VZV PCR. As in our patient, angiographic analysis typically demonstrates segmental constriction, often with small and large arteries affected. ¹

As demonstrated by our case, diagnostic testing for CNS varicella infections should be interpreted with respect to the infection time course. In vasculitis, VZV DNA is typically detected early in the disease course, and after 7 days may not be detected in the CSF. ² In contrast, there usually is a delay in the formation and presence of anti-VZV IgG antibodies in the CSF, which have been detected after 14–50 days. ¹ The narrow window of PCR positivity is likely why detection of anti-VZV IgG antibodies in the CSF can be more sensitive in diagnosing VZV vasculopathy than detection of DNA. ^1,3 Given concurrent psychiatric comorbid illness in our patient, getting an accurate daily history and detecting subtle changes in mental status was difficult. He likely had a more chronic VZV CNS infection, explaining the negative CSF VZV PCR and positive VZV IgG test.

Our case also emphasizes that HIV-infected patients are at risk for nontraditional hospital onset infections, and the wide-ranging manifestations of VZV reactivation, including vasculopathy and retinal necrosis. ¹ Clinicians should thus consider virus reactivation as a cause of hospital onset infections among patients with HIV, be aware of typical CNS imaging findings, and recognize the utility of CSF IgG testing in diagnosing CNS varicella disease.