No relevant financial disclosures Gilden D, et al Neurol. - - PowerPoint PPT Presentation

Is VZV the cause of GCA? AAS = CON

ALFREDO A. SADUN, MD, PhD

Flora Thornton Chair Doheny Eye Institute Vice-Chair of Ophthalmology, UCLA

NANOS March 5, 2018

No relevant financial disclosures

Gilden D, et al Neurol. Neuroimmunol Neuroinflamm. 2016

• Studied temporal artery (TA) biopsies
• 104 were GCA+ (positive)
• 100 were GCA- (negative)
• 61 TA from (normal) at autopsy
• Varicela-zoster virus (VZV) antigens found in 74% of GCA +
• VZV antigens found in only 58% of GCA –
• VZV antigens found in only 18% autopsy (nl) TA

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What does the paper conclude?

• 1) That VZV and histological changes may “help to

explain disease (GCA) pathogenesis”

• 2) GCA may result from trans-axonal transport of

reactivated VZV from ganglia to TA wall.

• 3) There may be a milder form of GCA both explaining
• That inflammation may be restricted to the adventitia
• That the GCA- cases had a 58% chance of VZV

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Strengths of the paper

• Many cases
• A second form of controls (patients not even suspected
• f GCA)
• A strong P value between the suspicion of GCA and

VZV antibodies

• A lot of work

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What does the paper actually show?

• VZV antigen, in comparison to autopsy cases, was
• about 4 times more likely to be present in the vessel wall of

GCA + cases

• About 3.2 times more likely GCA- cases
• VZV antigen near areas of adventitial inflammation

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That VZV was

• 4 X higher in TAB GCA + compared to controls
• 3.2 X higher in TAB GCA – compared to controls
• Makes sense if both had different forms of GCA

But that 18% of autopsy cases showed VZV is very problematic unless we say that 18% of the elderly have subclinical VZV arteritis

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There is no causal role of VZV in GCA

• Association does not prove causality

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There is no causal role of VZV in GCA

• Association does not prove causality
• Other studies did not find VZV in TAB specimens
• Helweg-Larsen et al 0/13 GCA+
• Kennedy et al 0/15
• Rodriguez-Pla 0/50

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There is no causal role of VZV in GCA

• Lack of clinically supportive data
• Only 4% of GCA was preceded by VZV (Rhee et al)

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There is no causal role of VZV in GCA

• Interventions to decrease VZV reactivation have not

decreased rates of GCA

• VZV vaccination have decreased VZV but not GCA

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It does not warrant a sea change in our way of considering or treating GCA

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I had the chance to review a review paper in press by Kedar & Berger. They emphasize that Gilden et al is at level 5 class evidence.

Association does not prove causality

• VZV may be an artifact of
• Their staining process (remember J. Lawton Smith who

published many different ophthalmological conditions with spirochetes (syphilis).

• The altered immune state of GCA
• A myriad of other possibilities

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1969: Down a similar road for cause of uveitis

• Treponema pallidum demonstrated in the aqueous

humor of eyes with idiopathic uveitis

• Silver stain
• Retraction after it was noted that using the glass

stopped bottle demonstrated spirochete like shavings of glass in every application

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We’ve been down this road before in GCA

• Burkholderia isolated from temporal arteries of 10 GCA
• NANOS 2016 Bradley Katz et al presented:

Absence of Bacteria in the Temporal Arteries of Patients with Giant Cell Arteritis. 18 TABs as f/u of previous linkage to Burkholderia 16S rRNA sequencing failed to identify any bacterial DNA

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Why does it matter if VZV is the cause? If it were true we should be:

• Treating GCA recurrence by adding antivirals
• Be much less aggressive in the use of steroids or other

immunosuppression

• This is currently not warranted.

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Conclusion: VZV is not the cause of GCA

• At best, there is an association
• A) Artifactual
• B) Surrogate marker
• C) Population at risk for both
• At worst this is just the most recent premature

conclusion in a series of studies purporting to find the underlying pathology of GCA.

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We need to continue investigating the pathophysiology of this remarkable disease.

• Since VZV is NOT the cause of GCA

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