HPV vaccine and lupus – bad expert testimony in a lawsuit

In a lawsuit filed with a court in Israel a young girl and her mother are suing, apparently (since I do not have the lawsuit, I’m reporting based on a news report that included an interview with the girl’s mother) claiming that the girl was negligently administered an HPV vaccine because the family was not warned that it can trigger an autoimmune disease, lupus. Because the evidence does not support the claim that there is a link between the HPV vaccine and lupus, the claim is unfounded, and should be rejected. The Ministry of Health is not required – and should not – warn parents about risks vaccines do not have: that would be misleading those parents.

The case

From the news article about the case, it appears that on 17 December 2014, thirteen year old Doron Cohen got the first dose of the HPV vaccine. After that, claims the family, she developed “neurological symptoms” such as weakness of her eyes or legs.”

Medical experts examining her found no link between the HPV vaccine and lupus. On 21 January 2015, Ms. Cohen received the second dose, and in the article, the family criticized giving her that dose without asking if there were any medical issues in the interim. The Ministry of Health said that “before the second dose a notification was sent, per procedure. No report of health changes or adverse reactions after first dose was received by the [school] nurse.”

The family filed a tort suit, claiming a failure to warn of the risk of triggering an autoimmune disease. Apparently, there was a family history of lupus – the mother’s sister has it.

Are HPV vaccine and lupus (and other autoimmune diseases) linked?

The answer, from multiple sources, is a pretty clear no. Dr. Gil Chapnick, described in the article as a “pediatrician and professional adviser to Mida’at, a volunteer organization of doctors, scientists and public advocates working to promote public health,” explained this in the original article:

In monitoring tens of millions of people who got the vaccine it was found that the rate of various diseases, including lupus, has not gone up. Current medical knowledge clearly shows that there is no link between getting an HPV vaccine and the appearance of various problems, lupus included.”  [Editor’s note – all translations from the article are my own. D.R. ]

Dr. Paul Offit, a vaccine expert, also recently reviewed data from four different studies that together covered over a million women, some of which received HPV vaccines, some of which did not.  The studies found no difference in the rates of autoimmune diseases between women who got the vaccine and women who did not. The vaccine did not increase the risk of autoimmune diseases, including lupus. Dr. Offit goes on to explain:

These data shouldn’t be surprising. To date, researchers have not found evidence that meets any of the four operational criteria necessary to prove that HPV vaccines induce autoimmunity.

To make such a connection, the following criteria must be met:

  • First, investigators must show that one or more of the L1 proteins that comprise HPV4 mimic self-antigens (see Note 1) and that self-antigen–specific T or B cells are present in the circulation.
  • Second, self-antigens must be present in quantities necessary to evoke autoimmune responses. The HPV4 vaccine contains 20 µg, 40 µg, 40 µg, and 20 µg of the L1 proteins from HPV serotypes 6, 11, 16, and 18, respectively. That is not likely to be enough protein to induce autoimmunity. Another way to look at this would be to note the differences between Lyme disease and Lyme vaccine. Lyme disease causes autoimmune arthritis, but Lyme vaccine doesn’t, even though the Lyme vaccine contains a protein that mimics a self-antigen. Lyme bacteria replicate in joints, generating large amounts of self-proteins. The Lyme vaccine (LYMErix™), on the other hand, contained only 30 µg of the outer surface A protein, which—although it mimicked the LFA-1 self-antigen—wasn’t enough to induce autoimmunity.
  • Third, costimulatory signals, cytokines, and other activation signals (see Note 2) produced by antigen-presenting cells like dendritic cells are necessary to drive autoimmune responses. Although live viruses and bacteria can drive these responses at levels necessary to induce autoimmunity, inactivated viruses or purified proteins don’t drive these response nearly as strongly—at least not without a powerful adjuvant, like squalene or oil-in-water emulsions.
  • Fourth, peripheral tolerance mechanisms, which the body uses to prevent autoimmune responses from the moment of birth, must fail. Again, no evidence for breaking tolerance has been shown for HPV vaccines.

As Dr. Offit discussed, the science clearly shows no link. The news story mentioned that a discussion of the Israeli Advisory Committee of Infectious Diseases and Vaccines, which included experienced doctors, also concluded that there was no support to the claim of a link between autoimmune diseases and HPV vaccines (pdf).

Problematic expert opinion

So, with studies showing no link between HPV vaccines and autoimmune diseases, monitoring of tens of millions of doses in various countries finding none, and experts seeing no basis for such a link, what basis is there for the case to go forward? After all, the ministry of health only needs to warn of a risk of autoimmune disease if it exists, and the case against such a link is incredibly strong.

Enter Yehuda Shoenfeld.

Shoenfeld is an established, respected medical authority in Israel. He is described in the article as “an expert in internal medicine and clinical immunology, editor of the main medical journal in Israel, Harefua (The Medicine), and chief of an internal medicine division in Sheba Hospital in Tel Hashomer for many years. Today he directs the Center for Autoimmune Diseases in that hospital. Prof. Shoenfeld also served on science committees for the Ministry of Health, the Ministry of Science, and the Association for Fighting Cancer.”

A well-credentialed medical authority in Israel, Dr. Shoenfeld made a number of claims to justify a need to warn Ms. Cohen’s parents of a risk between HPV vaccines and lupus. He claimed that:

  • There was a known link in the medical literature between getting HPV vaccines and getting lupus.
  • The active ingredient in the vaccine likely led to the disease, based on –
    1. The girl being healthy prior to getting the vaccine.
    2. Precedents in the medical literature.

With so much data against his claim, what is Dr.. Shoenfeld referring to, and should his views carry weight?

Over the past few decades, Dr. Shoenfeld appeared to have subscribed to a belief that various vaccines cause autoimmune diseases. Dr. Shoenfeld has served as expert witness in multiple cases before the vaccine court in the United States (link to NVICP post). But in recent years his claims in such cases were rejected, and his opinion on this is not accepted in the scientific community. Why?

Dr. Shoenfeld bases his claims of a link between HPV vaccines and autoimmune diseases on a syndrome he calls ASIA, “Autoimmune Syndrome Induced by Adjuvants.” But that syndrome, as we discussed previously, is not accepted by the scientific and medical community, was rejected by the United States vaccine court, and should not be accepted by the Israeli courts, either. What’s wrong with it?

  1. ASIA is badly defined. Its criteria are so vague that it makes it really hard to use it as a tool to diagnose a real problem.
  2. ASIA is only supported by very, very limited data. Basically, it is based on a small number of case studies – so few, that they do not show much – and mice studies and cells in the lab studies.
  3. That limited data, in this context, is used to try and counter the studies with over a million subjctsthat have found no link between HPV vaccines and autoimmune diseases.

So when Dr. Shoenfeld is claiming that the medical literature supports a link, and that there are precedents, he is trying to counter large scale, carefully controlled studies in over a million people, combined with data in tens of millions more vaccine recipients, with his own badly defined theory relying on a limited range of publications (most of them in journals where he himself is a member of the editorial board) using scant data. That’s untenable. His claims simply cannot stand.

These criticisms were described, as explained in previous posts, by scientist/surgeon blogger Orac, in a scientific article written by researcher Dave Hawkes, and by the United States National Vaccine Injury Compensation Program (NVICP), the vaccine court. Beyond the previously discussed decision in NVICP, which did not address an HPV case, Prof. Shoenfeld provided testimony similar to that he provided in the Cohen case in an HPV case in the United States.

In Rowan v. Sec’y of HHS, 2014 U.S. Claims LEXIS 1436 a plaintiff claimed the human papillomavirus (“HPV”) vaccines that his daughter, Natalie Rowan, received made her seriously ill with migraine and muscle weakness. Dr. Shoenfeld testified as an expert witness and claimed that ASIA was the undiagnosed cause of her symptoms.  Id. at 16.  Dr. Shoenfeld testified that it was the “aluminum adjuvant in the HPV vaccine” which induced the petitioner’s chronic fatigue and headaches via ASIA.   Id. at 21. However, NVICP rejected the claim on two grounds. First, Dr. Shoenfeld provided no evidence from the petitioner’s medical report that supported the aluminum theory. Second, the special master noted that ASIA is not a proven theory by any means.  Id. at 16.  The court held the plaintiff failed to meet her burden of proof because she failed to show by preponderance of the evidence that the HPV vaccine was the actual cause of her injuries.  Id. at 50.  The court also soundly rejected Dr. Shoenfeld’s ASIA in that case.

Dr. Shoenfeld’s credentials are impressive, but credentials are not data. Dr. Shoenfeld’s view that HPV vaccines cause autoimmune diseases is not just not supported by the data: it is directly countered by it.

Since there is no real support for a link between HPV vaccines and autoimmune diseases, and plenty of evidence against it, the Ministry of Health should not have warned Ms. Cohen’s parents of such a link: warning against a non-existent risk would have been misleading them, and unfair.

In my opinion, by encouraging families, against all evidence, to blame the vaccine for their children’s illnesses, those promoting the ill-founded claim that the HPV vaccine and lupus, along with other autoimmune diseases, are linked are doing those families a wrong. These families end up facing extensive skepticism and disbelief from those aware of the data, which can only add to their distress in dealing with a sick child. They are very unlikely to win in court, and a loss would add to their burden.

Not only do these claims hurt the families of those suffering autoimmune diseases in multiple ways, they have an additional cost: they may scare others from protecting their children against potentially fatal or deeply harmful HPV infections. These claims help no one, and only set up the stage for unnecessary tragedy. Israeli courts, scientists, and other, should send a loud, clear message that will protect the most people by clearly rejecting this and similar claims.

Notes

  1. In autoimmune diseases, the immune system sometimes is incapable of discriminating between “self-antigens,” that is, antigens that are on every cell in the body, and external antigens. Immune systems generally can distinguish self antigens from external ones.
  2. As discussed in this article, the pathway to induce an immune response is quite complicated. Lots of signal molecules, like cytokines, induce the system to attack foreign bodies with antigens that trigger the immune response.

This article is by Dorit Rubinstein Reiss, Professor of Law at the University of California Hastings College of the Law (San Francisco, CA), is a frequent contributor to this and many other blogs, providing in-depth, and intellectually stimulating, articles about vaccines, medical issues, social policy and the law. 

Professor Reiss writes extensively in law journals about the social and legal policies of vaccination. Additionally, Reiss is also member of the Parent Advisory Board of Voices for Vaccines, a parent-led organization that supports and advocates for on-time vaccination and the reduction of vaccine-preventable disease.

 
 

 

Dorit Rubinstein Reiss
This article is by Dorit Rubinstein Reiss, Professor of Law at the University of California Hastings College of the Law (San Francisco, CA), is a frequent contributor to this and many other blogs, providing in-depth, and intellectually stimulating, articles about vaccines, medical issues, social policy and the law. 

Professor Reiss writes extensively in law journals about the social and legal policies of vaccination. Additionally, Reiss is also member of the Parent Advisory Board of Voices for Vaccines, a parent-led organization that supports and advocates for on-time vaccination and the reduction of vaccine-preventable disease.