Examining the Role of VZV in Giant Cell Arteritis

February 19, 2016

The Rheumatology Journal Club will explore the connection between polymyalgia rheumatic, giant cell arteritis (GCA) and the varicella-zoster virus during its Feb. 25 Twitter chat.

This week the Rheumatology Journal Club Twitter chat will explore the connection between polymyalgia rheumatic, giant cell arteritis (GCA) and the varicella-zoster virus (VZV).

The chat will feature Maria A. Nagel, M.D., an author of the February 2015 study in Neurology that explored the connection between the varicella-zoster virus and giant cell arteritis (GCA), a form of vasculitis that can lead to the inflammation of blood vessels, in particular, the temporal arteries.

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, of 711,000 Americans with polymyalgia rheumatic, approximately 228,000 have giant cell arteritis. It primarily affects Caucasian women over the age of 50 and is most often treated with corticosteroids.

The Neurology study is the work of Don Gilden, M.D., and Dr. Nagel, both of the University of Colorado. Dr. Gilden’s research on the varicella-zoster virus dates back to 1978. His work exploring the connection between the varicella-zoster virus and giant cell arteritis was first published in 1998.[[{"type":"media","view_mode":"media_crop","fid":"46114","attributes":{"alt":"Maria Nagel, M.D.","class":"media-image media-image-right","id":"media_crop_4277310527395","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5327","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"Maria Nagel, M.D.","typeof":"foaf:Image"}}]]

The 2015 study in Neurology suggests that the varicella-zoster virus (VZV), which is most often associated with chickenpox in children or shingles (herpes zoster) in adults, could be responsible for the inflammatory cascade that leads to giant cell arteritis.

The study found that 61 of 82 (74 percent) of giant cell arteritis-positive temporal artery (TA) biopsies obtained postmortem, were positive for the varicella-zoster virus as compared to a control group of one in 13, or 8 percent.

The Gilden-Nagel team isn’t the only group that has made this connection. In 2001, writing in the journal Investigative Ophthalmology & Visual Science, Bradley M. Mitchell and Ramon L. Font found a significant association of varicella-zoster virus DNA to temporal artery biopsy samples positive for giant cell arteritis as compared with the negative specimens. However, they found that the virus is present at “extremely low quantities, is abortively replicating, or is latent.” For years, other studies confirmed those results, until 2013 when, writing in the journal Neurology, Dr. Nagel (who will participate in Thursday’s chat) wrote about a suspected link between the varicella zoster virus vasculopathy and giant cell arteritis in five patients.

Researchers suspect that after a childhood chickenpox infection, the varicella-zoster virus could reactivate itself late in life possibly leading to the inflammatory process associated with giant cell arteritis. But still, there is no definitive link between the varicella-zoster virus and giant cell arteritis, said John Cowdery, M.D., an emeritus professor of medicine at the University of Iowa and a member of the Rheumatology NetworkEditorial Board.

“VZV can lie dormant in the trigeminal ganglion and reactivation of the virus may result in a zoster outspread that appears in the path of nerve. This reactivation may be sporadic or associated with conditions such as immunosuppressive, cancer or infection. Finding the VZV antigen in a high percentage of biopsies is very suggestive, but falls short of cause-effect,” he said.

Dr. Cowdery questions whether the inflammatory process associated with giant cell arteritis, or perhaps prednisone therapy, could lead to local reactivation.

In terms of treatment, Gilden and Nagel suggest the addition of antiviral treatment to corticosteroids.

“Because GCA seems to be a VZV vasculopathy primarily affecting the TA, treatment of GCA patients with corticosteroids and IV acyclovir, as recommended for intracerebral VZV vasculopathy, is likely to be the most effective therapy and may shorten the length of treatment with corticosteroids. It remains unclear whether standard oral antiviral agents (e.g., valacyclovir, 1 g, 3 times daily for 2–4 weeks) in conjunction with corticosteroids will be as effective as IV acyclovir and corticosteroids; dosage and duration of treatment also remain to be determined,” they wrote in the study.

Writing in a November 2015 issue of JAMA Neurology, Dr. Nagel and colleagues again called for antiviral treatment, which may “confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.”

But others caution it is too early to say that everyone with giant cell arteritis should be treated with antivirals.

“I do not believe this paper can justify the addition of acyclovir to corticosteroids as the authors suggest. Given the nature of response/relapse in GCA it would likely take a large number of patients and a number of years to document a beneficial effect of acyclovir.

“Here’s a thought:  We’re now routinely vaccinating against VZV. If a retrospective study of a large database could show that VZV vaccination resulted in a reduced incidence of GCA -  then that would be a more convincing link,” Dr. Cowdery said.

 

The Rheumatology Journal Club will host its next Twitter chat Thursday, Feb. 25 with two hour-long sessions at 4 p.m. and 10 p.m. EST.

Featured study:  "Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis," February 18, 2015, Neurology.

Participate in the Twitter chat via #RheumJC

 

References:

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS),

"Questions and Answers about Polymyalgia Rheumatica and Giant Cell Arteritis"

 Don Gilden, Teresa White, et al.

"Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis,"

Neurology. Published online before print February 18, 2015. doi:http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000001409 Mitchell BM, Font RL.

"Detection of varicella zoster virus DNA in some patients with giant cell arteritis,"

IOVS Journal. 2001 Oct;42(11):2572-7.  Gilden D1, Nagel MA.

"Varicella zoster virus and giant cell arteritis,"

urrent Opinion in Infectious Diseases. 2016 Feb 11. [Epub ahead of print]  Nagel MA, Bennett JL, Khmeleva N, Choe A, Rempe A, Boyer PJ, Gilden D.

"Multifocal VZV vasculopathy with temporal artery infection mimics giant cell arteritis,"

Neurology. 2013 May 28;80(22):2017-21. doi: 10.1212/WNL.0b013e318294b477. Epub 2013 May 1. Nagel MA, White T, et al.

"Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis,"  

JAMA Neurology.  2015 Nov;72(11):1281-7. doi: 10.1001/jamaneurol.2015.2101.  Gilden D1, Nagel MA.

"Varicella zoster virus and giant cell arteritis,"

Current Opinion in Infectious Diseases. 2016 Feb 11. [Epub ahead of print]