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Biologic Infusions

Nearly as soon as the mRNA COVID-19 vaccines from Pfizer and Moderna were granted emergency use authorization in the United States and started rolling out in other countries around the world, questions arose about their link with allergic reactions in some recipients, including anaphylactic (very serious and even life-threatening) reactions.

We encourage you to check out our main guide: Can You Safely Get a COVID-19 Vaccine If You Have a History of Allergic Reactions? for a basic overview.

The U.S. Centers for Disease Control and Prevention (CDC) has been closely following the vaccine rollout and monitoring allergic reactions to provide more specific guidance.

In a recent update, the CDC now advises that it “considers a history of any immediate allergic reaction to any other vaccine or injectable therapy (i.e., intramuscular, intravenous, or subcutaneous vaccines or therapies not related to a component of mRNA COVID-19 vaccines or polysorbate) a precaution but not a contraindication to vaccination for both the Pfizer-BioNTech and Moderna COVID-19 vaccines.”

This has led to questions from members of the CreakyJoints and Global Healthy Living Foundation communities who take or have taken infusion or injection medications for chronic conditions such as rheumatoid arthritis, axial spondyloarthritis, inflammatory bowel disease, psoriasis and psoriatic arthritis, and lupus.

What if you’ve had an injection-site or infusion-site reaction to these medications in the past? Does that mean you shouldn’t get a COVID-19 vaccine?

The answer is not necessarily a simple yes or no. If you have questions about this issue, you should speak to your rheumatologist or the health care provider who manages your chronic conditions to talk about your medical history and decide what is right for you.

We spoke with rheumatology and allergy experts for general guidance, but this is not a substitute for personal medical advice.

How Common Are Allergic Reactions, Including Anaphylaxis, to the COVID-19 Vaccine?

The answer is reassuring: Allergic reactions are not common and anaphylactic reactions are very rare. The CDC recently published a report of the data they gathered from people who received a Pfizer COVID-19 vaccine between December 14 and 23, 2020. There were 21 cases of anaphylaxis and 83 cases of non-anaphylaxis allergic reaction after administration of 1,893,360 first doses of the Pfizer COVID-19 vaccine.

Anaphylaxis cases

  • 86% of anaphylaxis cases had symptom onset within 30 minutes of vaccination
  • 81% anaphylaxis cases of had a history of allergies or allergic reactions, including some with previous anaphylaxis events
  • 90% of anaphylaxis cases were treated with epinephrine as part of therapy and no deaths have been reported

Non-anaphylaxis cases

  • 87% of non-anaphylactic cases were classified as nonserious
  • 85% of non-anaphylactic cases had a symptom onset within 30 minutes of vaccination
  • 67% non-anaphylactic cases had a past history of allergies or allergic reactions

The CDC advises that people who meet the following criteria should not get either the Pfizer or Moderna COVID-19 vaccine at this time:

  • Severe allergic reaction (anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components
  • Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including polyethylene glycol [PEG])*
  • Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with the vaccine ingredient PEG)*

* The CDC says these groups should not receive mRNA COVID-19 vaccination at this time unless they have been evaluated by an allergist-immunologist and it is determined that the person can safely receive the vaccine (such as under observation, in a setting with advanced medical care available).

Why Is the CDC Recommending Caution If You’ve Had Allergic Reactions to Infused or Injectable Medications?

First, let’s be clear:

  • The CDC is NOT saying that people who take infused or injectable medications should not get a COVID-19 vaccine.
  • The CDC is NOT saying that all people who have had allergic reactions to infused or injectable medications should not get a COVID-19 vaccine.

What they are saying: If you’ve had an immediate allergic reaction to an infused or injectable medication — such as a biologic for an inflammatory or autoimmune disease — you should consider as a precaution and discuss it with your doctor.

The CDC says: “These persons should be counseled about the unknown risks of developing a severe allergic reaction and balance these risks against the benefits of vaccination.”

The American College of Allergy, Asthma & Immunology (ACAAI) says to consider these questions:

  • Do you have a history of severe allergic reaction to an injectable medication (intravenous, intramuscular, or subcutaneous)?
  • Do you have a history of a severe allergic reaction to a prior vaccine?
  • Do you have a history of a severe allergic reaction to polyethylene glycol (PEG), a polysorbate or polyoxyl 35 castor oil (e.g. paclitaxel) containing injectable or vaccine?

“We recommend that these questions be asked and if anyone answers yes, that they be referred to a board-certified allergy and asthma doctor,” says allergist Mary Hudelson, MD, a member of the ACAAI COVID-19 Task Force.

PEG is found in a number of products, from creams to laxatives, and medications like the injectable steroid Depo-Medrol, says Dr. Hudelson.

Many injectable or infused medications also contain polysorbate. This is why the CDC and the ACAAI are urging caution about getting the COVID-19 vaccine if you’ve had a severe allergic reaction to an injectable or infused medication in the past.

“Polysorbate, PEG, and castor oil can all cross-react,” says Dr. Hudelson. “The COVID-19 vaccine contains PEG to stabilize the lipids that surround the mRNA that helps get it to the cell, and that’s suspected as a cause of allergic reactions, though more research is needed. Because the vaccine is brand new, we went ahead and included people with polysorbate and castor oil allergies in our guidance to be more cautious.”

However, polysorbate and PEG are used at different molecular weights in various products. Having a reaction to one molecular weight of PEG doesn’t guarantee you’ll have a reaction to a different molecular weight, which is why it’s important to speak to an allergist for guidance.

“The doctor will consider a very detailed history of the reactions you’ve had to previous vaccines or biologic drugs, the severity of the reaction, and your risk factors for severe illness from COVID-19,” says Dr. Hudelson. “It’s a doctor-patient shared decision-making to determine the risk of getting COVID-19 versus a potential allergic reaction to the vaccine, and which you’re more likely to tolerate.”

Allergic Reactions vs. Side Effects from an Infused or Injectable Medication

The CDC recommends you ask your doctor about the COVID-19 vaccine if you have had an immediate allergic reaction, even if it was not severe, to a vaccine or injectable therapy for another disease.

Keep in mind that “systemic side effects of biologics are different mechanisms than allergic symptoms,” says Dr. Hudelson. “A severe allergic reaction is going to include low blood pressure, shortness of breath, and other symptoms related to the release of histamine that is causing this reaction to get worse and worse.”

According to Johns Hopkins Medicine, signs of a biologic medication allergic reaction include:

  • Shortness of breath
  • Chills
  • Redness
  • Itchiness (like itchy eyes or itchy lips)
  • Redness, itchiness, or warmth and tenderness at the injection site
  • Full body rash

“We need to determine if a patient has had an anaphylactic reaction to an infused or injected medication. They should likely avoid COVID-19 vaccines for now. For people with milder reactions, it is more of a risk versus benefit decision-making process,” says Nilanjana Bose, MD, a board-certified rheumatologist with the Rheumatology Center of Houston.

If you’re not sure whether your side effects after receiving an infused or injected medication are considered an allergic reaction, ask your doctor.

Infliximab (Remicade) and Rituximab (Rituxan): Recognizing Allergic Reactions

Any infused or injectable medication could possibly cause an allergic reaction (as can common over-the-counter ones; after all, some people are allergic to Tylenol or Advil).

But some medications may be more likely to cause reactions than others. Two common biologics to be aware of are infliximab (Remicade) and rituximab (Rituxan).

Infliximab (Remicade) is a commonly prescribed biologic that can cause allergic reactions in some patients. Symptoms of a reaction during or after the infusion include:

  • Hives
  • Difficulty breathing
  • Chest pain
  • High or low blood pressure
  • Fever and chills

Symptoms of a delayed allergic reaction (three to 12 days after infusion) include:

  • Fever
  • Rash
  • Headache
  • Sore throat
  • Muscle or joint pain
  • Swelling of the face and hands
  • Difficulty swallowing

Rituximab (Rituxan) is a different biologic medication and infusion-related reactions are common side effects. Symptoms include:

  • Hives (red itchy welts) or rash
  • Itching
  • Swelling of your lips, tongue, throat, or face
  • Sudden cough
  • Shortness of breath, difficulty breathing, or wheezing
  • Weakness
  • Dizziness or feel faint
  • Palpitations (feel like your heart is racing or fluttering)
  • Chest pain

Recognizing Allergic Reactions to a COVID-19 Vaccine

Allergic reactions to the COVID-19 vaccine would generally fall into one of two categories: non-severe immediate reactions and severe reactions, per the CDC.

Non-severe reactions that occur within four hours of getting vaccinated are know as immediate allergic reactions.  Symptoms include:

  • Hives
  • Swelling
  • Wheezing

Severe allergic reactions require treatment with epinephrine or an EpiPen, or treatment at a hospital, according to the CDC. This is also known as anaphylaxis. Symptoms include:

  • Hives
  • Low blood pressure
  • Constriction of airways
  • Wheezing (respiratory distress)
  • Swollen tongue or throat
  • A weak and rapid pulse
  • Nausea, vomiting, or diarrhea
  • Loss of consciousness

The CDC recommends that people who have had a severe reaction to the first vaccine not receive a second dose. Those who had a non-severe immediate reaction to the first dose should not receive a second dose unless they’ve been evaluated and cleared by an allergist-immunologist.

Precautions for Getting a COVID-19 Vaccine If You’ve Had Reactions to Infused or Injected Medications

If you and your health care provider decide that you should get a COVID-19 vaccine but you have experienced reactions to infused or injectable medications in the past, there are some precautions to take when you go in for the vaccine.

First, make sure to let the person giving you the vaccine know about the medications you take. They will likely have you wait for 30 minutes after receiving the vaccine for monitoring.

Even if you typically use allergy medications like Benadryl before getting your biologic infusion, it’s a good idea not to do so before your COVID-19 vaccine. The CDC recommends against this because antihistamines do not prevent anaphylaxis, and their use may mask “cutaneous” (skin) symptoms, which could lead to a delay in the diagnosis and management of anaphylaxis.

“The first symptoms of allergic reactions to vaccines often involve the skin, such as with hives,” says Dr. Hudelson. “So if you have an allergic reaction and you’ve already taken Benadryl ahead of time, you’ll block the histamine and we’re not going to see that skin rash. The allergic reaction will have progressed a lot further along when you start to show symptoms, so we won’t be able to treat it with epinephrine as quickly as we might want to.”

The CDC states that fever- and pain-reducing medications, such as acetaminophen (Tylenol) or ibuprofen (Advil) can be taken to treat local or systemic symptoms after your vaccine, if medically appropriate. However, taking these medications ahead of the vaccine for the purpose of preventing post-vaccination symptoms is not currently recommended.

Monitor your symptoms closely after you get the COVID-19 vaccine and call your doctor if any side effects are concerning or do not seem to be going away after a few days.

Here’s more information about what to do after getting a COVID-19 if you’re immunocompromised.

“Thankfully, allergic reactions are very rare,” says Leah Alon, MD, a rheumatologist in New York City. “But apart from those rare cases, I would highly recommend all my other patients to receive a COVID-19 vaccine as soon as possible. The COVID-19 vaccines are generally considered safe in the patients with autoimmune diseases and are very important to protect them, especially if they are on immunosuppressive drugs that could make them more prone to severe infections.”

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ACAAI Guidance on Risk of Allergic Reactions to mRNA COVID-19 Vaccines. American College of Allergy, Asthma & Immunology. January 8, 2021. https://college.acaai.org/acaai-guidance-on-risk-of-allergic-reactions-to-mrna-covid-19-vaccines-2/.

Allergic reactions to vaccines. UpToDate. January 8, 2021. https://www.uptodate.com/contents/allergic-reactions-to-vaccines.

 CDC COVID-19 Response Team; Food and Drug Administration. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020. Morbidity and Mortality Weekly Report. January 15, 2021. doi: http://dx.doi.org/10.15585/mmwr.mm7002e1. 

Choquette D, et al. Incidence and Management of Infusion Reactions to Infliximab in a Prospective Real-world Community Registry. The Journal of Rheumatology. July 1, 2015. doi: https://doi.org/10.3899/jrheum.140538.

Coronavirus disease 2019 (COVID-19): Vaccines to prevent SARS-CoV-2 infection. UpToDate. January 8, 2021. https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-vaccines-to-prevent-sars-cov-2-infection.

 COVID-19 Vaccines and Allergic Reactions. U.S. Centers for Disease Control and Prevention. December 31, 2020. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/allergic-reaction.html.

Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States. Vaccines & Immunizations. U.S. Centers for Disease Control and Prevention. January 6, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html.

Interim Considerations: Preparing for the Potential Management of Anaphylaxis After COVID-19 Vaccination. Vaccines & Immunizations. U.S. Centers for Disease Control and Prevention. December 31, 2020. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html.

Interview with Leah Alon, MD, a rheumatologist in New York City

Interview with Mary Hudelson, MD, an allergist and member of the American College of Allergy, Asthma, and Immunology COVID-19 Task Force

Interview with Nilanjana Bose, MD, a board-certified rheumatologist with the Rheumatology Center of Houston

Important Safety Information. Remicade. https://www.remicade.com/important-safety-information.html.

Important Side Effect Information. Rituxan. https://www.rituxan.com.

Kati PM, et al. Clinical review: Serious adverse events associated with the use of rituximab – a critical care perspective. Critical Care. August 31, 2012. doi: https://doi.org/10.1186/cc11304.

Medication Information Sheet for Remicade. Dartmouth-Hitchcock Inflammatory Bowel Disease Center. Accessed January 15, 2020. https://www.dartmouth-hitchcock.org/documents/Info_sheet_Remicade.pdf.

Pfizer-BioNTech COVID-19 Vaccine. Rheumatology Solutions. Accessed January 15, 2021. https://www.arthritis-sa.com/blog/pfizer-biontech-covid-19-vaccine.

Side Effects of Biologic Medications. Johns Hopkins Arthritis Center. January 12, 2016. https://www.hopkinsarthritis.org/arthritis-news/side-effects-of-biologic-medications.