Ep 130: A 27-Year-Old with Penicillin Allergy

A young woman with a history of penicillin allergy and an indication for penicillin treatment.  The discussion focuses on mechanisms of penicillin allergy and the utility of desensitization.

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Transcript

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[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

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[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Wiener and we're joining you from the Johns Hopkins School of Medicine. Welcome to Harrison's Podclass, episode 130: a 27-year-old with a penicillin allergy. Cathy, today we're seeing a 27-year-old woman who's eight weeks pregnant and was recently diagnosed with primary syphilis. Cathy, the best treatment? 

[Dr. Handy] Penicillin. 

[Dr. Wiener] Correct but she reports to you that she has a history of penicillin allergy. On further questioning, she tells you that when she was 15 years old, she was diagnosed with strep throat, and upon taking amoxicillin, she developed diffuse itching, wheezing, and throat tightness that required an emergency room visit where they gave her an epinephrine shot and told her that she was truly allergic to penicillin. The rest of her past medical history is unremarkable and she takes no medications. 

[Dr. Handy] This is a bit difficult because currently the only approved therapy for syphilis in pregnant women is penicillin, and that's because other agents, such as ceftriaxone, which may treat the infection in the mom, is not effective in treating the fetus. The treponemes can cross the placenta and infect the fetus. 

[Dr. Wiener] Yep, that's where this question is going. Okay, so the question's going to ask you, which of the following statements regarding penicillin allergy is true? Option A. children with unconfirmed low-risk penicillin allergy should receive desensitization therapy. Option B. desensitization therapy will be effective in this patient, but will have to be repeated if she ever requires penicillin treatment again. Option C. over 50% of patients involved in healthcare report a penicillin allergy. Option D. serum-specific IgE antibodies to penicillin are found in allergic patients with high sensitivity, but low specificity. And option E. is type IV immune reactions result from the activation of mast cells and basophils through IgE-dependent and independent mechanisms. 

[Dr. Handy] All right, lots to cover here. Let's start by saying that the patients reporting penicillin allergy is remarkably common, but it's definitely not over 50%. It's more like 10 to 20% of patients report an allergy. 

[Dr. Wiener] Okay, so we've ruled out C. as not true. 

[Dr. Handy] Yes but the use of the term allergy is imprecise. Acute or immediate reactions occur during or within one to six hours of drug exposure, and delayed reactions occur six hours to several days or weeks after drug exposure. Reactions can be mild, which usually refers to just affecting one organ; they can be moderate, affecting two or more organs; or we consider them severe when they're associated with changes in vital signs. Furthermore, the symptom presentation depends on the mechanisms of the reactions. Acute reactions are typically called type I and are IgE-dependent, IgE-independent, or cytokine-release reactions, and they are mediated by activation of mast cells and basophils. 

[Dr. Wiener] Okay, so E. is not true, either. 

[Dr. Handy] Right, delayed reactions are not IgE-mediated. So this would include type II antibody-mediated cytotoxicity, type III immune complex-mediated reactions, and type IV reactions. Type IV reactions include benign reactions, which are typically skin-limited, but can also include severe cutaneous reactions, and that would be things like Stevens-Johnson syndrome, or toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms, or DRESS. 

[Dr. Wiener] And that last group that you talked about, type IV reactions, they're typical of the rash that many people get after a few days of beta-lactams, right? 

[Dr. Handy] Correct, and those are not anaphylaxis responses that we really worry about. 

[Dr. Wiener] Okay, so option D. which said, serum-specific IgE antibodies to penicillin are found in allergic patients with high sensitivity, but low specificity, is looking at diagnosis. What about that one? 

[Dr. Handy] So that's not true, either. The reverse is actually true. Unfortunately, serum-specific IgE antibodies to penicillin are found in allergic patients, but they have low sensitivity, meaning that there are more false negatives but it does have a high specificity, meaning that there are fewer false positive results. 

[Dr. Wiener] Are there any other diagnostic options? 

[Dr. Handy] Yes, that's complicated, and maybe we can do that on a future episode, but briefly, you can do skin testing. Anaphylaxis to penicillin has not been reported in skin test-negative patients. The basophil activation test provides evidence of IgE sensitization by challenging the patient's basophils in vitro with the culprit drug, eliminating the need for direct skin tests, which has a small risk for anaphylaxis. Also, type I responses are associated with elevation of serum tryptase, a specific biomarker of anaphylaxis released from mast cells and basophil granules. Tryptase levels above the normal range or above a patient's baseline obtained within 30 minutes to four hours of initial symptoms are diagnostic of type I and mixed reactions. 

[Dr. Wiener] Okay, well, our answer has to do with desensitization, so let's bring it home. 

[Dr. Handy] Well, first, option A. is incorrect. Children with unconfirmed low-risk penicillin allergy do not require desensitization therapy. Single-dose oral challenges have been shown to be safe in children and adults at low risk for penicillin allergy. Those with unconfirmed allergy labels should also be de-labeled. 

[Dr. Wiener] Okay, that leaves us with the correct answer being option B. 

[Dr. Handy] Yes, desensitization therapy will be effective in this patient, but it will have to be repeated if she ever requires penicillin treatment again. 

[Dr. Wiener] I'm surprised. It's not permanent? 

[Dr. Handy] No, IgE-mediated desensitization takes advantage of inhibitory mast cell or basophil pathways, which are activated by low doses of drug antigens. Desensitized patients have transient conversion from positive to negative skin tests. Desensitization is a temporary phenomenon which does not lead to sustained tolerance and must be repeated with each exposure or if there has been a pause between doses equal to two or more half-lives of the drug. 

[Dr. Wiener] Wow! Okay, so the teaching point of this case is that penicillin allergy is common, but fortunately, most people do not have a type I or anaphylactic response. Those responses are typically mediated by IgE. In patients with documented type I response to penicillin, drug desensitization is safe and effective but is not permanent. 

[Dr. Handy] And you can find this question and other questions like it in the Harrison's Self-Review book. And if you want to read more on desensitization, you can check out the Harrison's chapter. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's. And thank you so much for listening. If you enjoyed this episode, please leave us a review, so we can reach more listeners just like you. 

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