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As we continue to learn more about how individuals with inflammatory disease respond to the COVID-19 vaccine, preliminary new research shows that some people with autoimmune inflammatory rheumatic diseases (AIIRD) have experienced herpes zoster reactivation — also known as shingles — after receiving the Pfizer vaccine.
However, it’s important to note that this research does not prove that the vaccine causes shingles, as the observational study design was not structured to determine a causal relationship.
And experts want to emphasize how important it is for people with inflammatory rheumatic diseases to get vaccinated (more on this below) against COVID-19.
Israeli researchers were monitoring for post-vaccination side effects in a group of 491 patients with autoimmune inflammatory rheumatic diseases (from two different rheumatology departments) and compared them to side effects experienced by 99 healthy control subjects.
Shortly after receiving the vaccine, 1.2 percent of patients with AIIRD (six patients total) developed their first case of shingles compared to none of the controls, per an April 2021 report in the journal Rheumatology.
- Four of the six affected individuals had rheumatoid arthritis
- One had Sjögren’s syndrome
- One had undifferentiated connective disease
In five out of the six cases, the AIIRD patients developed shingles shortly after the first vaccine dose (the patients who went on to complete the second vaccine dose did not have other adverse effects). In one case, shingles infection occurred after the second dose.
The majority of shingles cases were mild, except for one case involving the eye in a rheumatoid arthritis patient being treated with tofacitinib (Xeljanz), a type of medication known as a JAK inhibitor. Five patients received antiviral treatment for shingles, and all of the patients’ shingles symptoms resolved within six weeks.
The varicella-zoster virus, which causes chickenpox, also leads to shingles. After you’ve had chickenpox, the virus lies dormant in the nerve tissue near your spinal cord and brain, but may reactivate as shingles years later, per the Mayo Clinic.
Here is a breakdown of each of the six cases the researchers observed.
Case 1: A 44-year-old woman with a history of Sjögren’s syndrome and treated with hydroxychloroquine presented with a case of shingles after COVID-19 vaccination. She had a history of chickenpox (caused by the same virus that leads to shingles) and was not vaccinated against shingles. Three days after her first dose of the vaccine, she developed a skin rash along with low back pain and headache. She did not receive shingles treatment and her symptoms resolved within three weeks. No rheumatic disease flare was reported during this time period.
Case 2: A 56-year-old woman with a history of seropositive rheumatoid arthritis (meaning the blood has antibodies that attack the body and inflame joints) had a case of shingles involving the eye. Her RA had been treated with multiple biologics and she had low disease activity while taking tofacitinib (Xeljanz), which she started in 2014. This patient had a history of chickenpox and was not vaccinated against shingles. Four days after the Pfizer shot, she developed symptoms including severe pain in her left eye and forehead. An eye exam revealed that she had hyperemic conjunctivitis (a result of shingles affecting the eye). She was treated with the antiviral drug acyclovir for 14 days, lubricant eye drops, and painkillers. Her symptoms gradually resolved within six weeks, and her treatment with tofacitinib was temporarily discontinued for two weeks — but she did not experience an arthritis flare during that time.
Case 3: A 59-year-old woman with seropositive rheumatoid arthritis experienced a shingles episode after COVID-19 vaccination. She had tried multiple biologics and baricitinib (Olumiant), a JAK inhibitor, and was being treated with the JAK inhibitor upadacitinib (Rinvoq) and the corticosteroid prednisone (5 mg per day) with a partial response. She had a history of chickenpox and received the shingles vaccine before she started baricitinib in 2019. Two days after her second dose of the Pfizer COVID-19 vaccine, she developed shingles symptoms including pain and skin rash. This patient was treated with the antiviral drug valacyclovir for three days, but it was discontinued because of side effects. Upadacitinib was discontinued when shingles was detected, which was followed by a severe flare of rheumatoid arthritis. Her skin lesions slowly healed within six weeks, and her anti-rheumatic therapy was switched to etanercept (Enbrel).
Case 4: A 36-year-old woman with seropositive rheumatoid arthritis complicated by interstitial lung disease, which causes the scarring of lung tissue, presented with shingles after COVID-19 vaccination. Her antirheumatic treatment included the disease-modifying drug mycophenolate mofetil (CellCept), the biologic rituximab (Rituxan), and prednisone (7 mg per day). She had a history of chickenpox and was not vaccinated for shingles. Ten days after her first dose of the Pfizer vaccine, she developed pain and skin rash, and was treated with acyclovir for one week. Her symptoms resolved within six weeks, and she received the second dose of the vaccine without any adverse effects. No rheumatoid disease flare was reported during this period.
Case 5: A 38-year-old woman with undifferentiated connective tissue disease and antiphospholipid syndrome (APS) who was treated with hydroxychloroquine and aspirin had an episode of shingles after COVID-19 vaccination. She had a history of chickenpox and was not vaccinated against shingles. Two weeks after her first dose, she developed tingling, itching, and a skin rash. She was prescribed acyclovir for one week, and her symptoms resolved within three weeks. She received the second dose without any other adverse effects, and did not experience any flare of her baseline disease during that period.
Case 6: A 61-year-old woman with seropositive rheumatoid arthritis being treated with tocilizumab (Actemra) and prednisone (5 mg per day) had her first episode of shingles after COVID-19 vaccination. She had a history of chickenpox and was not vaccinated for shingles. Two weeks after her first Pfizer vaccine dose, a typical shingles rash appeared and she was treated with valacyclovir for one week. She completely recovered within 10 days, but she also experienced a mild arthritis flare and the dose of prednisone was increased to 7.5 mg per day. She received the second COVID-19 vaccine dose as scheduled without any other adverse effects.
“In all cases, the baseline rheumatic disease was either mild or stable under medical treatment,” the researchers noted.
What Could Be Causing Singles in These Patients?
Researchers don’t yet know, but it’s important to keep in mind that this is a very small number of patients and the data is preliminary. This study does not prove that the COVID-19 vaccine causes shingles in people with inflammatory or autoimmune conditions.
“It’s a good observational study, but there are issues with observational studies in general — there are a lot of confounding factors,” says Masoom Modi, MD, a rheumatologist at UCLA Health Porter Ranch, who was not involved with the study. “This is a certain population that obviously has a lower immune system and therefore an increased risk to get any type of infection. However, we can’t really conclude that the COVID-19 vaccine caused shingles.”
More research will be needed to understand if there is an association between the COVID-19 vaccine and the reactivation of the shingles virus, or whether there are additional factors that may play a role for certain patients.
The risk of shingles infection is estimated to be two-fold higher in rheumatoid arthritis patients compared to the general population (most of the patients in this study had RA). Additional risk factors for shingles infection in rheumatoid arthritis include old age, high disease activity, and dose-related use of glucocorticoids (not present in these particular patients).
There doesn’t appear to be an increased risk of shingles after other types of vaccines, but certain medications can raise the risk, like the drug tofacitinib (Xeljanz) — used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis, says Dr. Modi.
“Some of the original studies did show an increased risk of shingles for that treatment, and one of the patients in this new study had been on tofacitinib,” she says. “But while there might be some increased risk if you are on a certain medication, this study does not say there is a link between the two.”
It’s Important to Get the COVID-19 Vaccine
Of course, many of these patients did not receive the shingles vaccine, which helps prevent shingles recurrence. What’s more, experts like Dr. Modi hope this study does not discourage COVID-19 vaccination.
“In this case, there were only six patients and the shingles cases were mostly mild,” says Dr. Modi. “If there is a link, which I don’t think we can really extrapolate from this data, it shouldn’t prevent someone from getting the COVID-19 vaccine because we can treat your zoster, but we don’t know how your COVID-19 is going to manifest if you get it.”
In other words, even if there is a very small risk of getting shingles after your COVID-19 vaccine if you have AIIRD (which this study does not prove), it doesn’t outweigh the benefit of being protected against COVID-19 and its potential outcomes.
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Furer V, et al. Herpes zoster following BNT162b2 mRNA Covid-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series. Rheumatology. April 12, 2021. https://doi.org/10.1093/rheumatology/keab345.
Interview with Masoom Modi, MD, a rheumatologist at UCLA Health Porter Ranch
Shingles. Mayo Clinic. October 6, 2020. https://www.mayoclinic.org/diseases-conditions/shingles/symptoms-causes/syc-20353054.