Silence is patronizing: infections, vaccinations & Polymyalgia rheumatica
As a vaccine fan girl, I struggled to write this post. In the process of searching for the scientific evidence on the underlying disease mechanisms in Polymyalgia rheumatica, I found a vaccine hot potato, and my knee jerk reaction was to fling it as far away from myself as possible. (To learn more about Polymyalgia rheumatica, you can read its work-in-progress Diagnosis Description here.) I was naively hoping to entirely side-step vaccinations as a correlated factor in autoimmune disease (first proposed in 2011 as the controversial Autoimmune Syndrome Induced by Adjuvants (ASIA)). I briefly considered not writing about these studies at all. I realized I had to brave my discomfort with this subject because I can be a vaccine fan girl AND know that selective silence is patronizing. So, I’ll stumble on as accurately as I can.
The Fan Girl Makes the Case for Vaccination
Vaccines are beneficial—and essential—for populations as a whole, with widespread health benefits for the majority of individuals within those populations. Vaccinations work when populations as a whole use them to protect everyone. Vaccines have been responsible for the most lives saved of any other medical advance. I readily recognize that certain individuals do not tolerate certain vaccinations—and that those side effects can have serious consequences to those individuals. For those that don’t tolerate certain vaccinations well, it’s even more important that the community around them is vaccinated, in order to protect those that cannot be vaccinated against circulating disease.
There Are Some Drawbacks & I’m Not An Expert
Sometimes individuals who won’t tolerate a particular vaccine well can be identified prior to vaccination, but sometimes they cannot be identified beforehand. And this is where the benefits to the population as a whole collide with the, sometimes unpredictable, costs to certain individuals. It’s also why we have reporting processes and databases for adverse events after vaccination. In the U.S., it’s why we all get that information sheet following any vaccine administered. If only we had similar databases for infection reporting and autoimmune disease correlation…I can dream.
Healthcare vaccine communication relies on a lot of efficient shorthand—what’s good for the population is good for the individual (true in the vast majority of cases, but not all). Amplifying uncertainty surrounding vaccines can have devastating consequences to populations—representing many, many, many, individuals—so we hesitate to discuss it, especially when we’re not experts. Not only do we not want to discuss it, we also tend to want to shut down the conversation completely. As a non-expert, this is what I immediately wanted to do after reading these studies. Shut. It. Down. Shutting down discourse breeds mistrust. So, here goes.
I can theorize how a vaccine, along with genetic susceptibility, could trigger autoimmune disease, in much the same way an infection could be an environmental trigger for autoimmune disease. This theoretical reaction could be significantly delayed, due to the action of the adaptive (or learned) immune system, making it difficult to correlate the autoimmune reaction to the vaccine. Add in the lack of definitive diagnostic criteria with most autoimmune diseases, average delays in diagnosis, and it becomes difficult to study a correlation between vaccinations and autoimmune disease. Especially when autoimmune diseases are almost universally under-studied, and many are considered rare. Theories are not evidence. But if no one is looking for a correlation, then how can we be confident in the lack of a correlation in a vaccine’s safety profile? I can pose that question, but I don’t have the expertise to answer it. Polymyalgia rheumatica, COVID-19 vaccination/infection, and influenza vaccination/infection present a unique confluence of commonness that has been studied, so I’ll just present the straightforward evidence.
Polymyalgia rheumatica & COVID-19 Vaccines
After reports in France of Giant cell arteritis (GCA) occurring after COVID-19 vaccination, Mettler et. al set out to study Giant cell arteritis and Polymyalgia rheumatica (two autoimmune diseases that often occur together) in connection with the COVID-19 vaccine. Mettler et. al used
VigiBase (https://www.who-umc.org/vigibase/vigibase/), the WHO global individual case safety report database, which contains spontaneous reports of suspected adverse drug reactions collected by national drug authorities in >130 countries. (2022)
They compared VigiBase adverse reports for COVID-19 vaccinations with adverse reports for influenza vaccinations. They found:
“1,295,482 reports concerned COVID-19 vaccines, among which we observed 147 GCA cases, 290 PMR cases and 9 GCA with PMR cases.”
317,687 reports concerned influenza vaccines, among which they observed 78 Giant cell arteritis cases, 303 Polymyalgia rheumatica cases, and 14 cases of Giant cell arteritis with Polymyalgia rheumatica.
The overall number of adverse reports for influenza vaccination were lower than the overall adverse reports for COVID-19 vaccination. So, proportionally, the reports of Polymyalgia rheumatica after influenza vaccination were higher. Because of this, the authors concluded that COVID-19 vaccination is less correlated with adverse reports of Polymyalgia rheumatica and Giant cell arteritis following vaccination, compared to adverse reports following influenza vaccination. But the COVID-19 vaccine may still be correlated with Polymyalgia rheumatica—causation cannot be assumed with this study design:
Overall, our study supports a potential safety signal for GCA and PMR with COVID-19 vaccines. Further data are needed to confirm this signal. Nevertheless, COVID-19 vaccine benefits dramatically outweigh this potential risk, which appears very rare relative to the billions of doses administered so far.
They also describe a shorter time frame (several days) between COVID-19 vaccination and onset of symptoms, compared to influenza vaccination and onset of symptoms found in a separate study.
Polymyalgia rheumatica & COVID-19 Infection
If there’s a risk of developing Polymyalgia rheumatica following COVID-19 vaccination, is there a risk of developing Polymyalgia rheumatica following COVID-19 infection? Chang et. al studied the occurrence of new-onset autoimmune diseases following COVID-19 infection using a non-governmental healthcare database called TriNetX. They included 3,814,479 (unvaccinated) participants in their study spanning the period between January 1st, 2020 and December 31st, 2021. Of over 3 million participants:
888,463 participants had a laboratory confirmed case of COVID-19
2,926,016 participants, who acted as controls, did not have a laboratory confirmed case of COVID-19
compared to the control group, the risk of developing polymyalgia rheumatica was almost three times as high following laboratory confirmed COVID-19 infection
The evidence this study presents regarding the risks of developing new-onset Polymyalgia rheumatica following COVID-19 infection is compelling. A question that occurs to me: Does COVID-19 vaccination have a comparatively protective effect against developing new-onset Polymyalgia rheumatica, or not? More studies are necessary for a vaccinated population who later contracts COVID-19, but it would be difficult to determine from such a study what degree the infection or the vaccine contributed to the development of Polymyalgia rheumatica.
Polymyalgia rheumatica & Influenza Vaccination
In addition to the VigiBase study summarized above, a very small 2021 study and literature review looked at Polymyalgia rheumatica and Giant cell arteritis in conjunction with influenza vaccination. Their inclusion criteria was defined as subjects that developed Polymyalgia rheumatica and/or Giant cell arteritis up to one month after influenza vaccination. Liozon et. al (2021) found that six patients with Polymyalgia rheumatica fit their criteria for post-influenza vaccination disease and
(Human Leukocyte Antigen) HLA-DRB1*13:01 haplotype was more frequently associated with post-influenza vaccine cases of Polymyalgia rhuematica and Giant cell arteritis
post-influenza vaccine cases of Polymyalgia rheumatica tended to be “self-limited” compared to post-influenza vaccine cases of Giant cell arteritis, which demonstrated a more prolonged, relapsing course.
Polymyalgia rheumatica & Influenza Infection
Falsetti et. al (I know, I know, I looked up his University affiliation) studied 58 participants with Polymyalgia rheumatica to determine whether infections and/or vaccinations were considered triggering events. “Fifteen patients (26%) with PMR described a connection with environmental agents:”
environmental agents were considered relevant if they occurred three months prior to symptom onset.
environmental agents were included in this study when “the patient him- or herself judged this event as correlated to his or her symptoms.”
four participants reported influenza vaccination within the three months prior to symptom onset.
five participants reported seasonal influenza infection within the three months prior to symptom onset.
a significant correlation was found between the “presence of an environmental trigger and shorter time to normalize inflammation” with steroid treatment. There was also a lower frequency of gleno-humeral (shoulder) synovitis on ultrasound.
A sustained, very low dose of steroids (glucocorticoids) was necessary to avoid muscle pain symptoms in 10 out of 15 patients. This was more frequently the case in participants who reported an environmental trigger before the onset of Polymyalgia rheumatic.
(2020)
There are drawbacks to this study: its observational design, lack of control group, absence of noted lab confirmation of patient-reported infections. What it lacks is also what I like about it—that they took patient report of the connection as their inclusion criteria. Still, it excludes the patients who may have had influenza vaccination or infection, but for whatever reason, did not connect it to the later development of Polymyalgia rheumatica. This is a significant drawback to this study.
Why It Matters
Vaccine risk/benefit analysis is complex. People over 50, who are by definition, those who are susceptible to Polymyalgia rheumatica, are also those most at risk for severe complications, or death, from COVID-19 and Influenza. The average age for those with Polymyalgia rhuematica is 70, which is an age group even more at risk for severe complications from COVID-19 and influenza. High quality studies correlating influenza infection with Polymyalgia rheumatica diagnosis are notably absent. A comparison between the relative risk of a correlation between the influenza vaccine and new-onset Polymyalgia rheumatica, compared to the relative risk of influenza infection and new-onset Polymyalgia rheumatica, compared to the relative risk of both the vaccination and a later infection, is also absent. People with known risk factors: family history of Polymyalgia rheumatica and/or Giant cell arteritis, or a known variation in the Human Leukocyte Antigen HLA-DRB1*13:01 "*may* be at higher risk of developing Polymyalgia rheumatica following influenza vaccination, and should discuss this risk with their doctor. In stark contrast with COVID-19 and influenza, I found no documented cases of deaths resulting from a diagnosis of Polymyalgia rheumatica. Understanding potential vaccine risks is important. The vaccine fan girl still thinks the vaccine protection against severe, or fatal, COVID-19 and/or influenza infections is worth the small potential risk of developing non-fatal Polymyalgia rheumatica post-vaccination.
Next week, I’ll explore the association between Polymyalgia rheumatica and HLA-DRB1*13:01 in greater detail. For those who are new to AutoimmuneDx, I am currently writing posts based on reader-requests for more information and analysis on particular autoimmune diagnoses. If you would like me to take a closer look at a particular diagnosis, please leave a comment below. If you don’t feel comfortable commenting publicly, email me at autoimmunedx@gmail.com.
References
Chang R, Yen-Ting Chen T, Wang SI, Hung YM, Chen HY, Wei CJ. Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study. EClinicalMedicine. 2023 Feb;56:101783. doi: 10.1016/j.eclinm.2022.101783. Epub 2023 Jan 10. PMID: 36643619; PMCID: PMC9830133.
Falsetti P, Conticini E, Acciai C, Baldi C, Bardelli M, Gentileschi S, Cantarini L, Frediani B. Polymyalgia rheumatica following infective triggers or vaccinations: a different subset of disease? Reumatologia. 2020;58(2):76-80. doi: 10.5114/reum.2020.95360. Epub 2020 Apr 30. PMID: 32476679; PMCID: PMC7249527.
Liozon E, Parreau S, Filloux M, Dumonteil S, Gondran G, Bezanahary H, Ly KH, Fauchais AL. Giant cell arteritis or polymyalgia rheumatica after influenza vaccination: A study of 12 patients and a literature review. Autoimmun Rev. 2021 Feb;20(2):102732. doi: 10.1016/j.autrev.2020.102732. Epub 2020 Dec 14. PMID: 33326851.
Lundberg IE, Sharma A, Turesson C, Mohammad AJ. An update on polymyalgia rheumatica. J Intern Med. 2022 Nov;292(5):717-732. doi: 10.1111/joim.13525. Epub 2022 Jun 11. PMID: 35612524; PMCID: PMC9796644.
Mettler C, Jonville-Bera AP, Grandvuillemin A, Treluyer JM, Terrier B, Chouchana L. Risk of giant cell arteritis and polymyalgia rheumatica following COVID-19 vaccination: a global pharmacovigilance study. Rheumatology (Oxford). 2022 Feb 2;61(2):865-867. doi: 10.1093/rheumatology/keab756. PMID: 34626105.
Metyas S, Chen C, Aung T, Ballester A, Cheav S. Rheumatologic Manifestations of Post SARS-CoV-2 Infection: A Case Series. Curr Rheumatol Rev. 2022;18(4):346-351. doi: 10.2174/1573397118666220211155716. PMID: 35152867.