So many people have a penicillin allergy, don't they? Studies put the incidence at around 10%.^​[1]​ One in every ten people you meet are allergic to penicillin. It it were a disease, it would be one of the commonest, comparable to asthma or diabetes...

But penicillin is often the first line antibiotic recommended for infections. Why is this? Is this part of a conspiracy to hurt our patients? Or is penicillin allergy usually a myth?

A 2017 meta-analysis estimated that around 95% of those with a documented penicillin allergy are actually able to tolerate the antibiotic.^​[2]​

Another interesting statistic comes from a paper published in 2007.^​[3]​ In the 30 years from 1972 to 2007, around 100 million people in the UK were exposed to oral amoxicillin. The number of deaths due to penicillin anaphylaxis during this period? ... One

In terms of actual mortality risk, this is something akin to being crushed by a flying cow while you sleep. And the mortality risk of a penicillin allergy pales into insignificance compared to the risk of opening a bottle of champagne (24 deaths per year on average).

The paper

Today's paper is a review piece looking at the epidemiology and best management of penicillin allergy. The authors explain the dangers of failing to challenge a historical documented allergy and give some great advice on how to do this practically.

Shenoy E, Macy E, Rowe T, Blumenthal K. Evaluation and Management of Penicillin Allergy: A Review. JAMA 2019;321(2):188–99^​[4]​

Why 95% of penicillin allergies are not allergies

1. The commonest reaction is a delayed benign rash, likely a type IV hypersensitivity reaction. This type doesn't involve antibodies, and can be called a 'nonallergic' reaction. It may not recur on subsequent exposure to the allergen.

2. Even if the reaction was a type I hypersensitivity (IgE-mediated), this appears to wane over time. A study from 2012 estimated that around 80% of patients with this type of reaction became tolerant to the allergen over a decade.^​[5]​

3. Many of those with documented penicillin allergy never actually had an allergic reaction to penicillin at all, but had a viral rash, intolerance or other cause for their symptoms. A large number of reported reactions are simply not allergic and have been incorrectly labelled as such - nausea, diarrhoea, etc.

Why having a false label of 'penicillin allergy' is bad for patients

1. Penicillin is still the first line antibiotic of choice for many types of infections, including skin, abdomen and chest. A documented penicillin allergy often means patients are given a sub-optimal antibiotic, which may fail to adequately treat their infection

2. The antibiotic choices for penicillin-allergic patients often have a larger side effect profile than penicillins. Macrolides in particular are infamous for causing diarrhoea. There is also the risk of Clostridium difficile.

3. Patients with a documented penicillin allergy are often given broader-spectrum antibiotics, which serves to increase antimicrobial resistance. This leads to the evolution of 'superbugs' like MRSA, which is not only bad for your particular patient but for humanity as a whole...

What to do about it

The authors suggest the following...

If your patient has a low risk history, perform a 'Direct Amoxicillin Challenge' - give them a 500mg tablet of amoxicillin and observe them for one hour. The absence of symptoms after this time demonstrates penicillin tolerance (i.e. no allergy).

What is a low risk history?

• Itch without rash


• Gastrointestinal symptoms


• Other non-allergic symptoms (emotions, dizziness, pain, etc)


• Family history of penicillin allergy only (no personal experience)


• History of remote or unknown reaction (over 10 years ago)

I think these would cover most of our patients! A direct challenge could be safely performed in the ED, while waiting for other test results. The patient's GP can then be informed, and this allergy can be removed from their file. It's important to do this because patients carry the label of 'penicillin allergy' throughout their lives and, as I sometimes tell patients: "Penicillin might save your life one day."

How about patients with more severe reactions?

Those with a 'moderate risk' history (urticarial rash, swelling or other features of IgE-mediated hypersensitivity) should be referred for skin testing followed by amoxicillin challenge. This obviously cannot be done during a visit to the Emergency Department, but could be suggested to the patient as an option they may not be aware of.

For those with a 'high risk' history (anaphylaxis), referral can be made to a Immunologist, who may elect to offer desensitization in a controlled environment. Personally, I tend to just believe patients when they tell me they nearly died after taking penicillin once! I am happy to prescribe a different antibiotic in these cases.

What about children?

In children, less time has passed since their 'penicillin reaction' and so it is often easier to find out what exact features they had.

Parents may feel strongly that we should not question their child's allergy, because they have seen a rash with their own eyes. As mentioned above, however, a label of 'penicillin allergy' will follow this child for the next 70 years and so it is important to get it right.

Also, as anyone who has worked in paediatrics known, children get rashes all the time, most of which are viral exanthems.

A penicillin challenge could certainly be considered in most cases. A 2016 study of 818 children with documented penicillin allergy found that 94% of them were able to tolerate a provocation challenge and could have the allergy label removed from their records.^​[6]​

1. 
   
   
   

   Zhou L, Dhopeshwarkar N, Blumenthal K, Goss F, Topaz M, Slight S, et al. Drug allergies documented in electronic health records of a large healthcare system. Allergy [Internet] 2016;71(9):1305–13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26970431

   
   
   
   


2. 
   
   
   

   Sacco K, Bates A, Brigham T, Imam J, Burton M. Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta-analysis. Allergy [Internet] 2017;72(9):1288–96. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28370003

   
   
   
   


3. 
   
   
   

   Lee P, Shanson D. Results of a UK survey of fatal anaphylaxis after oral amoxicillin. J Antimicrob Chemother [Internet] 2007;60(5):1172–3. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17761735

   
   
   
   


4. 
   
   
   

   Shenoy E, Macy E, Rowe T, Blumenthal K. Evaluation and Management of Penicillin Allergy: A Review. JAMA [Internet] 2019;321(2):188–99. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30644987

   
   
   
   


5. 
   
   
   

   Macy E, Ho N. Multiple drug intolerance syndrome: prevalence, clinical characteristics, and management. Ann Allergy Asthma Immunol [Internet] 2012;108(2):88–93. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22289726

   
   
   
   


6. 
   
   
   

   Mill C, Primeau M, Medoff E, Lejtenyi C, O’Keefe A, Netchiporouk E, et al. Assessing the Diagnostic Properties of a Graded Oral Provocation Challenge for the Diagnosis of Immediate and Nonimmediate Reactions to Amoxicillin in Children. JAMA Pediatr [Internet] 2016;170(6):e160033. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27043788