It’s always the vaccines: Harold Ramis and autoimmune vasculitis

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Last week, one of my favorite comedians and filmmakers of all time passed away unexpectedly. I’m referring, of course, to Harold Ramis, whose work ranged from movies like National Lampoon’s Animal House (the first R-rated movie I ever saw, actually), to gems like Ghostbusters and and Groundhog Day. In fact, in retrospect, when I posted about Brian Hooker and the antivaccine movement trying to resurrect the hoary corpse of the conspiracy theory that the CDC is some how “covering up” data that would prove that the antivaccine cranks were right all along about mercury in vaccines as a cause of autism, I probably should have called it “Groundhog Day for Mercury.” The reason, of course, is that the movie Groundhog Day was about a TV meteorologist played by Bill Murray, who is forced to relive Groundhog Day over and over again, with no one aware of the time loop except for him. The difference between the antivaccine movement’s conspiracy theories about mercury and the movie, of course, is that in the movie Bill Murray’s character, having acquired wisdom and won over the girl, so to speak, finally breaks out of the time loop to wake up on the morning of February 3. Not so the antivaccine movement, which seems stuck in a perpetual time loop dating back to around 2004 or 2005.

I know the analogy isn’t perfect, but there’s another aspect of the antivaccine movement that I’ve pointed out many times that’s come up again in the wake of Harold Ramis’ death. No, antivaccinationists didn’t directly blame Harold Ramis’ death on vaccines (although I half-expected them to). They did, however, “wonder” about whether the condition that sickened him nearly four years ago, afflicted him the last few years of his life, and ultimately killed him, autoimmune vasculitis, is related to vaccines. Why? Because in the antivaccine movement, it’s always about the vaccines. Always. Even when it’s not about the vaccines, it’s about the vaccines, as demonstrated by this post on the antivaccine crank blog Age of Autism entitled Harold Ramis, Inflammatory Vasculitis and “Rare” Conditions by Wayne Rohde. Here’s a classic example of what we in the skeptic biz know as JAQing off:

So how did this horrible disease afflict Mr. Ramis? Dr. Waseem Mir, a rheumatologist at Lenox Hill Hospital in New York told CBS news that only 1% of the US population has this disease, making it extremely rare. However, Dr. Peter Merkel, a rheumatologist and director of Penn Vasculitis Center at the University of Penn medical school told CNN that “Mr. Ramis had one of 15 identified variants of vasculitis. None of these conditions individually affects more than 200,000 people in the US. But if you add them all up together, it’s not rare, and the chances are everybody knows somebody, directly or indirectly, that is affected.”

Now does that last sentence sound familiar? Maybe in discussions about vaccine injury? If two leading rheumatologists cannot agree whether or not this medical condition is rare, why not examine some previous medical cases of vasculitis?

In a paper presented by Tomljenovic and Shaw in 2012 regarding the death of two individuals who were administered the HPV vaccine, tissue samples of the brain led the authors to interpret the results as demonstrating an autoimmune cerebral vasculitis. Now, we can confidently assume that Mr. Ramis did not receive a Gardasil vaccine, but it does bring vaccinations into the question. Another study, published in 2009 by Birck, Kaelsch, et al, titled “ANCA-associated vasculitis following influenza vaccination: causal association or mere coincidence?” did not prove a causal association between influenza vaccine and vasculitis, but it did assert that in rare cases vaccination might induce vasculitic disease. Now we have the possibility that influenza vaccine might, under “rare” conditions, induce vasculitis.

Yep. To antivaccine activists, it’s the vaccines. It always was the vaccines. It will always be the vaccines. Unfortunately, searching for “Harold Ramis” and “vaccines” reveals that Mr. Rohde’s article has metastasized far and wide on the Internet and Facebook, as any good conspiracy theory would. As I said, there’s no real evidence. Indeed, Mr. Rohde cites a website, Vasculitis UK, as saying that “Flu and Pneumonia vaccines are not recommended for vasculitis patients.” That’s odd. I Googled until I found what must be the webpage on the Vasculitis UK website to which Rohde was referring, entitled, appropriately enough, Vaccinations. Guess what it says? (Here’s a hint: What it says reveals Mr. Kohle to be either profoundly ignorant or profoundly disingenuous—or both.) Surprise! Surprise! It says almost the exact opposite of what Mr. Rohde says it says. The reason for not recommending some vaccines has nothing to do with their causing or potentially exacerbating vasculitis and everything to do with a common trait among patients being treated for autoimmune vasculitis, namely immunosuppression:

Patients taking immune-suppressants should not receive live vaccines such as yellow fever, typhoid and measles.

Live vaccine contains a small amount of the infection itself. Under normal circumstances the patient can fight off this small amount of infection but this is not possible for the vasculitis patient. This will have implications for holidays in destinations and where live vaccines are recommended, eg Africa, Asia, and Latin America.

Flu and Pneumonia vaccines are recommended for vasculitis patients. These are not live vaccines. Where the patient is unsure about a particular vaccine it is important to speak to the doctor about this issue.

Note how it says “Flu and Pneumonia vaccines are recommended for vasculitis patients.” What are not recommended for vasculitis patients are live attenuated virus vaccines, such as the shingles vaccine, not because they cause or exacerbate vasculitis but because vasculitis patients are often immunocompromised as part of the treatment of their autoimmune condition! Live virus vaccines aren’t recommended for these patients for exactly the same reason they’re not recommended for cancer patients currently undergoing chemotherapy or other patients who require treatments that are immunosuppressive. Mr. Rohde’s article is extremely deceptive on this point, and just plain wrong. One wonders if he was intentionally so obtuse as not to recognize that the flu vaccines being warned against were only the live vaccines, such as Fluenz, which is used in the UK) and that the reason why live virus vaccines are not recommended for many vasculitis patients is because they are immunosuppressed, not because they have an autoimmune vasculitis!

Also in his risibly bad argument, Mr. Rohde cites two of our favorite newer antivaccine “scientists,” Lucija Tomljenovic and Christopher Shaw in perhaps one of their most ridiculous papers ever:

In a paper presented by Tomljenovic and Shaw in 2012 regarding the death of two individuals who were administered the HPV vaccine, tissue samples of the brain led the authors to interpret the results as demonstrating an autoimmune cerebral vasculitis. Now, we can confidently assume that Mr. Ramis did not receive a Gardasil vaccine, but it does bring vaccinations into the question.

No. It. Does. Not.

I analyzed that paper when it came out. It showed nothing of the sort. Tomljenovic and Shaw claimed to show was that somehow the HPV vaccine caused some sort of autoimmune cerebral vasculitis in a young woman who died due to an HPV protein depositing in the cerebral vasculature and leading to an antibody-mediated response. The details are in my post, but the CliffNotes version is this. There were two young women who died whose brain tissue Tomljenovic and Shaw got a hold of because the parents thought that Gardasil had killed their daughters because they had died weeks after receiving a dose of the HPV vaccine. In both cases, the autopsy didn’t show any abnormalities in the brain that could account for either girl’s unexpected death. If these girls had had an immune-based vasculitis, whatever the cause, serious enough to kill them, it should have been visible as severe inflammation in the brain tissues on normal H&E sections (sections stained with the usual blue and pink dye and no special immunohistochemical stains). Then, the IHC might reveal the potential cause. In one of the two cases, Tomljenovic and Shaw bemoaned how the pathologist didn’t use any specific antibodies for inflammatory markers but rather noted changes consistent with terminal ischemic-hypoxic encephalopathy. What that means is that the pathologist thought that the changes he observed were consistent with the brain’s having suffered a significant period of time with low blood flow right before death, a very common finding that a competent pathologist who does autopsies regularly should be able to identify on standard H&E microscopic sections.

So in the paper being cited by Mr. Rohde, what we have are non-pathologists, who clearly don’t know how to interpret common neuropathological findings, throwing every inflammation-related antibody in the book at the brain sections from these unfortunate deceased young women, and then concluding that there was some sort of neuroinflammation because they saw staining in the blood vessels in the brain. There’s one huge problem, though: Totally inadequate controls. Tomljenovic and Shaw’s findings could just as well have been due to nonspecific staining. Not only didn’t they examine sections of age-matched normal brains as controls (the very minimum they should have done), but they also neglected to do some very basic controls for any IHC experiment, as I described in detail when I blogged the study. In the other paper cited by Mr. Rohde, there is no good evidence that the flu vaccine causes autoimmune vasculitis. In fact, the authors conclude:

In the literature different subtypes of vasculitis have been repeatedly reported after influenza vaccination. Several trials in patients with preexisting auto-immune disease failed to indicate an increased risk for disease recurrence after influenza vaccination but these investigations might be underpowered to detect this very rare but relevant side effect. Although our report does not prove a causal association between vaccination and vasculitis, it seems possible that in rare cases vaccination might induce vasculitic disease.

“It seems possible”? “In rare cases”? This is thin gruel. Here’s what probably happened. The authors, however they noticed it, came across four cases of people with autoimmune vasculitis who were diagnosed after influenza vaccination. They did a literature search to see if there was any evidence that might suggest if the flu vaccine can induce such a vasculitis. They failed to find any. So they waffled at the end that “it seems possible” and excuse away the negative studies by calling them underpowered. Of course, even if it is “possible” that the flu vaccine can cause autoimmune vasculitis, the evidence presented suggests that such an event is very, very rare indeed. Basically, Mr. Wohle confused correlation with causation, as antivaccine activists are so wont to do.

Mr. Wohle finishes up by invoking—of course!—the Vaccine Court and cases compensated. It never ceases to amuse me how antivaccinationists hate the Vaccine Court when it doesn’t find what they want but have no problem dumpster diving into it to find cases they do want to use to demonize vaccines. Funny, though, how out of 15,000+ petitions, Mr. Wohle only found 20 related to vasculitis, and the four that he picked to list are thin gruel indeed.

It all just goes to show that, to antivaccine cranks, no matter what the disease is, it’s about the vaccines. It’s always—always—about the vaccines, and if there’s a dead celebrity whose disease can be abused to draw attention to your antivaccine views, so much the better.