Is VZV - nanosweb.org Meeting'/2018/REP SLIDES... · • 100 were GCA- (negative) •61 TA from...
Transcript of Is VZV - nanosweb.org Meeting'/2018/REP SLIDES... · • 100 were GCA- (negative) •61 TA from...
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
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 of 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
• 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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