Q:

10/30/2012
At recent local and national meetings, it has been stressed now that one should consider using epinpehrine for dermal type allergic reactions. Is this now a hard indication like throat closure, vascular, lung and GI system involvement? I assume for body wide hives and/or angioedema and not a localized rash to a food? Can you review which questionable symptoms are or are not an indication for Epi that we typically see on a food allergy action plan? If a child eats strawberries for example and gets some hives on their body and face this is a hard and fast rule of automatic use of Epi? Many in the past would use Benadryl alone. Parents are often concerned about unnecessary trips to the ER via ambulance rides costing $500-$750 after using epi for skin only reactions, when Benadryl may have sufficed, and some of them probably use Benadryl anyway despite our advice.

So is it necessary that all patients with hives/rash only to foods or other triggers should now carry and potentially epi even if they never had angioedema or any other systemic sign? Also, as regards to stinging insect allergic individuals with local reactions only, don't the insect parameters mention up to 17% risk of local reactors eventually having a systemic reaction? So should all patients with local insect reactions also carry an epi-pen also, not just dermal or true systemic reactors?

A:

Thank you for your inquiry.

Unfortunately, we cannot dogmatically answer your questions. These issues are very significant topics of debate at this time, and in great part depend upon clinical judgment. In fact, at the upcoming 2012 American College of Allergy, Asthma, and Immunology meeting this November, there will be a full conference devoted exactly to the issues that you are pointing out. It will be held as a Thursday night dinner symposium on November the 8th. It will be in the format of cases such as the ones you have described, highlighting the issue as to whether or not an automatic epinephrine injector should be prescribed and whether or not epinephrine should be administered. There will be a panel of people who have studied anaphylaxis and published in this area, and it is anticipated that there will be disagreements on these issues amongst such experts. In the past, there has certainly been such disagreement.

What we can do for sure is recommend some published articles which act as guidelines in this regard, and share with you some principles that govern the prescription for and use of epinephrine in these situations.

One of the most important principles is that the treatment of anaphylaxis is epinephrine. It is the only acceptable first-line therapy. All of the articles and guidelines written in this area agree on this principle. Therefore, when you feel that there is a bona fide risk of anaphylaxis, even if the full-blown event has not occurred, epinephrine should be administered.

The reason for this is that anaphylaxis can start simply as a cutaneous response and progress rapidly to death within minutes. For example, in Pumphreys series of deaths (1), which is probably the largest series ever published, the median time for cardiac or respiratory arrest after the onset of symptoms (which were often cutaneous only) was 5 minutes for an iatrogenic reaction, 15 minutes for an insect sting, and 30 minutes for foods. In addition, in Paul Greenberger’s et al series of deaths, in greater than 50% of those recorded, death occurred within the first 60 minutes after the onset of symptoms (2). That is why every guideline published states quite clearly that epinephrine is the drug of choice, and the only frontline drug used to treat an anaphylactic event or an event that may progress to anaphylaxis (3, 4, 5, and 6).

The question then becomes as to which patients who manifest hives only might be subject to an episode rapidly progressing to an anaphylactic event.

There is no dogmatic answer for this, but quite clearly we have situations which would mandate the administration of epinephrine, and some in which there is perhaps leeway based upon your own personal clinical judgment.

For example, a child who has experienced an anaphylactic reaction to peanut, and who ingests peanut and develops hives, even though hives are the only manifestation at that moment, should receive an injection of epinephrine. Another example of this is a patient who is in your office and manifests hives after receiving an allergy injection (6).

There is more debate regarding a child as you mentioned who has hives after eating strawberries.

As mentioned, I can therefore not give you dogmatic answers, but we do have more specific guidelines as to when epinephrine should be administered. These are discussed in the Sampson (7) reference noted below. This reference summarized the deliberations of an NIAID and Food Allergy and Anaphylaxis Network-sponsored meeting of a panel of experts in this area. The meeting was designed to define anaphylaxis in terms of what manifestations were required to mandate an epinephrine injection. This article deals with the situations you mentioned as best we can at this time. But even this article, which was a result of four days of meetings of a worldwide panel of experts, clearly states that there would be exceptions to the rules mentioned. Therefore clinical judgment still remains important. Nonetheless, I highly recommend your taking a look at this work.

As to the issue of prescribing an automatic epinephrine injector to a patient with local reactions, again, this remains a matter of clinical judgment. Actually, the risk of a systemic reaction in a patient who experiences a large local reaction is no more than 5 to 10% (8). In fact, it states in this parameter that “The vast majority of patients who have had a large local reaction do not need to be tested for specific IgE antibodies to insect venom.” The guidelines also states, “In patients who have had large local reactions, it is optional to prescribe injectable epinephrine for use if the patient experiences a systemic reaction in the future.”

Therefore, as mentioned above, this scenario, as some of the other possible scenarios in regards to other potential settings where a patient may be at risk for anaphylaxis, is really dealt with according to one’s own clinical judgment. There are simply not enough data to allow us to make definitive decisions in all of these cases.

Thank you again for your inquiry and we hope this response is helpful to you.

References:
1.Pumphreys RSH. The lessons for management of anaphylaxis from a study of fatal reactions. Clinical and Experimental Allergy 2000; 30(8):1144-1150.

2.Greenberger, et al. Fatal anaphylaxis: postmortem findings and associated comorbid diseases. Annals of Allergy, Asthma, and Immunology 2007; 98:252-257.

3.Boyce JA, Assa’ad A, Burks AW, et al; NIAID-Sponsored Expert Panel. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-Sponsored Expert Panel. J Allergy Clin Immunol. 2010; 126(6 suppl):S1-S58.

4.Burks AW, Tang M, Sicherer S, et al. ICON: food allergy. J Allergy Clin Immunol. 2012; 129(4):906-920.

5.Lieberman P, Nicklas RA, Oppenheimer J, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010; 126(3):477-480.

6.Simons FE, Ardusso LR, Bilò MB, et al; World Allergy Organization. World Allergy Organization anaphylaxis guidelines: summary. J Allergy Clin Immunol. 2011; 127(3):587-593.

7.Sampson HA, et al. Second symposium on the definition and management of anaphylaxis: Summary Report - Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium. J Allergy Clin Immunol 2006; 117(2):391-397.

8.Golden D, et al. Stinging insect hypersensitivity: a practice parameter update. J Allergy Clin Immunol 2011; 127:852-854.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology