Q&A: Joint task force updates anaphylaxis practice parameter
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Key takeaways:
- New research informed 48 recommendations and nine key points.
- Shared decision-making can guide whether patients need to call 911 after a reaction.
- Tryptase measurements can aid in diagnosis.
A joint task force has published an updated, evidence-based practice parameter for diagnosing and treating anaphylaxis in Annals of Allergy, Asthma & Immunology.
The practice parameter focuses on seven areas where new evidence and recommendations have emerged. It also provides revised diagnostic criteria and defines anaphylaxis patterns.
Healio spoke with lead author and allergist David B.K. Golden, MDCM, associate professor, Johns Hopkins School of Medicine, to find out more.
Healio: How does this practice parameter build upon previous guidelines for anaphylaxis?
Golden: The last traditional practice parameter update on anaphylaxis was published in 2015. Many knowledge gaps were identified in that update, and most of them saw important advances in the following few years. The Joint Task Force on Practice Parameters (JTFPP) of the AAAAI and ACAAI had previously identified two specific questions for in-depth Grading of Recommendations, Assessment, Development and Evaluations (GRADE) analysis for an anaphylaxis practice parameter update that was published in 2020.
In its periodic review of possible update topics, the JTFPP was aware of areas that have had the most published research in the past 10 years supporting updated or new recommendations for clinical practice. The JTFPP’s workgroup identified seven areas in which they found the greatest impact of new publications: diagnosis, infants and toddlers, community settings, epinephrine autoinjectors, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, mast cell disorders and perioperative anaphylaxis.
Healio: Are there any specific changes or updates you would like to highlight?
Golden: There are 48 recommendations and nine key points in the document. I think they are all important and provide guidance to clinicians who evaluate and manage these patients, but four of them should get the most attention from allergists and others.
First, calling 911 or going to the ED may not be required if the patient experiences prompt, complete and durable response to treatment and has access to additional epinephrine autoinjectors.
Second, it is important to draw blood during a reaction for measurement of acute serum tryptase that can be compared with a later sample for baseline serum tryptase.
Next, the absolute risk for anaphylaxis remains small in patients on beta-blockers or ACE inhibitors, and shared decision-making is recommended to determine whether to make any change in medications or treatment plan. The risk is minimal during maintenance immunotherapy.
Finally, allergists should be aware of the connections between anaphylaxis and mast cell disorders, including mastocytosis and hereditary alpha-tryptasemia, and the approach to evaluation and management of these patients.
Healio: Could you provide some details about the change in the need for 911 calls and ED visits following anaphylaxis?
Golden: There are a lot of “ifs” in that recommendation. It is a conditional recommendation, which is a navigational signal for shared decision-making. The key word here is may. This is a very individualized decision that needs to be made between the patient and the doctor. It not only includes what we are saying in our guidance, but it also includes, as we say in shared decision-making, their values and preferences.
If the reaction is mild and you tell the patient that they don’t need to go to the ED or call 911, they might say that they would feel better if they went to the ED and got it checked. That is an individualized plan. The specific plan for each individual will be based on our guidelines and a lot of discussion.
Physicians need to go into the practice parameter and read the discussion about this updated recommendation. We included a color-coded graphic that provides guidance for patients and physicians in making these decisions.
For example, if the signs and symptoms that emerged prior to epinephrine administration resolved within minutes without recurrence, and the patient is asymptomatic, they can just stay at home and practice home observation. If patients have a few scattered hives or a little bit of rash, but everything else is getting better, it would be OK to stay home.
On the other hand, if signs and symptoms that emerged before epinephrine are improving or resolving, but they aren’t really gone, and there is some persistence of some mild throat discomfort, or nausea, or mild cough, it may be OK to stay at home and see if it continues to improve. But if it goes on for another 10 or 20 minutes, then it is time to call 911 and consider a second dose of epinephrine.
Then there are patients who previously have had a near fatal reaction or have needed more than one dose of epinephrine, and they are now having another reaction, but it is not that bad. They used their epinephrine, and they’re getting better. Should they call 911? Yes. Period. Because of the patient’s history.
There is specific guidance, but even that has to be individualized. There is a lot that goes into this guided decision-making.
Healio: Why are tryptase measurements so important to assessment and treatment planning?
Golden: There are two reasons.
First, you would be surprised how often cases are brought to us for review to determine if they were anaphylaxis. We review all the information, but it may be hard to tell. It is important to know if the serum tryptase level increases.
Tryptase is an enzyme. It is released by mast cells and basophils, along with histamine and other factors. When there is a reaction, tryptase is released into the system. It is easier to measure than histamine.
For about 15 years now, tryptase has been available to order as a blood test, ideally during the first hour, or 1 to 2 hours after the onset of the reaction, because it does gradually disappear. If the tryptase goes up, then it was anaphylaxis. If it doesn’t go up, then it probably wasn’t. But you also are going to have to do another tryptase measurement later, a so-called baseline level, because you have to know whether the level during the reaction actually went up.
The other reason is that if the baseline level is high, it may be an indication of an underlying mast cell condition, either mastocytosis or hereditary alpha-tryptasemia. These are conditions where the tryptase is high at all times, not just during a reaction. And those patients are at much higher risk for severe and fatal reactions.
Healio: Could you provide more details about the anaphylaxis risks for patients on beta-blockers, ACE inhibitors?
Golden: There is a lot of discussion about beta-blockers and ACE inhibitors because concern about these medications has been evolving for years. We previously addressed them in the 2015 practice parameter, and we commented on them again in our 2020 anaphylaxis GRADE guideline. But there has been new research in the past 2 or 3 years that helps us to realize that the danger is much smaller than we might have thought it was in the past. We have learned that these medications won’t cause someone to have anaphylaxis, but if patients do have anaphylaxis, it may be more severe. That’s important.
But the other side of the coin is that, in almost all cases, people are taking these medications for underlying cardiovascular disease. Changing or stopping these medications comes with risks too. So, what is the doctor to do? If someone has a food or insect allergy, should I write a letter to the cardiologist asking them to change medications because the patient could have severe anaphylaxis? I know from experience that the doctor is going to write me back and say, “Are you crazy? This patient needs to be on this medicine.” So, then I’m stuck and telling the patient that they need to be on this medicine but that they could also have a more severe reaction. This is something that has to be discussed with the patient and prescribing doctor.
This leads into a discussion of the difference between relative and absolute risk. Absolute risk is the chance of something happening. But relative risk is how much better or worse the risk may be. For example, what if being on these medicines made the risk for severe anaphylaxis two or three times higher? That sounds like a lot. But if the absolute risk is one in a million, and it goes three times higher, then it is still only three in a million. The absolute risk is still very, very low.
Healio: And how does immunotherapy play into these risks?
Golden: This really hits home with immunotherapy, like allergy shots. These risks have long been known. They’re in the package insert and in all previous guidelines. We used to say that if someone is on these medicines and can’t stop them, then they shouldn’t go into immunotherapy. Or if they want or need to stay on immunotherapy, then they shouldn’t take these medicines.
What we’re now saying is a little different. If they’re already on immunotherapy, the absolute risk from medicines for cardiovascular disease is so small that we now say they should not worry about it. These medicines are too important, and there is no need to change them. Patients who are on beta blockers for migraines, however, may be an exception. In that case, they should probably change the medicine, because there are alternatives.
Healio: How does the practice parameter address associations between anaphylaxis and mast cell disorders?
Golden: We’re bringing forward the idea that there is a previously unrecognized relationship between anaphylaxis, especially severe anaphylaxis, and mast cell disorders. Part of this goes back to our recommendations to measure tryptase. I was just on a conference call reviewing data for a research study, and we were complaining that the tryptase hadn’t been checked on almost half of the patients who had anaphylaxis. Why not?
Well, allergists haven’t been so aware of tryptase. It has only been able to be ordered as a blood test for about 15 years, which sounds like a long time. But it’s only in the past few years that doctors have become more aware of it because there has been more research. So, we thought that making allergists aware of this connection was very important.
If someone has anaphylaxis, check their tryptase. That’s one major step toward checking whether they have an underlying mast cell disorder. If they have hereditary alpha tryptasemia, the tryptase will be greater than 8. In the case of mastocytosis, elevated tryptase is one of the hallmarks.
Many doctors and most allergists really don’t know that mastocytosis can occur in people with normal tryptase, so it can be totally missed, and that’s an important thing not to miss.
There are other tests that can be done. In the practice parameter, we laid out a step-by-step approach. Make sure you do the tryptase. We’re trying to clue in doctors and allergists on what to look for and when to go further in checking for mastocytosis by doing additional blood tests or even a bone marrow biopsy.
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For more information:
David B.K. Golden, MDCM, can be reached at dbkgolden@gmail.com.