Penicillin allergy (amoxicillin hypersensitivity) in children

Is it sensitivity or allergy?

Practically speaking, it doesn’t matter as these can be considered synonymous in the context of penicillin.
Additionally, amoxicillin is a type of penicillin derivative, developed from the original penicillin compound.

What is the penicillin family and what types of antibiotics belong to this family?

Penicillin was discovered incidentally in 1928 by Alexander Fleming, in his laboratory.
It is an antibiotic that belongs to a larger group of antibiotics referred to as the beta-lactam group, named after their chemical structure, as they can destroy bacteria by inhibiting synthesis of their cell wall.

It is hard to exaggerate when talking about the effect this discovery had on human health, and as such the physicians that discovered and developed it received the Nobel prize for medicine in 1945.

So, penicillin was the first to be discovered but daily antibiotics such as amoxicillin and amoxicillin-clavulanate are derivatives of it and in fact improved versions of the original chemical structure of penicillin. These are very effective medications against a wide range of pediatric infections (respiratory, throat, ear, etc.), easily administered, safe and have an excellent side-effect profile.

How common is penicillin allergy?

As it is one of the most commonly used antibiotics in children (because it is so effective against common pediatric infections, the easiness of administration and the relatively low side effect profile) it is not surprising that it also has the highest rate of reported side effects. About 10-15% of the population carry the label “allergic to penicillin”. In practice, more than 90% of those classified as “allergic to penicillin” aren’t truly allergic to it. How does one explain this? There are two main reasons behind this:
# The first one is that this antibiotic is usually given to children during an acute infection. Most of the infections in children are viral, and often present with a rash during the infection or during recovery from the infection. When a rash develops 5 days after starting amoxicillin, there’s a high chance that the rash wasn’t caused by the medication but rather by the viral infection the child is or was suffering from (an example you can read about here is roseola).
# The second reason is that fortunately we have lots of reports that penicillin allergy has a high rate of resolution with age (80% of the cases resolve within 10 years).
That means, that if a 15 year old child presents to you with an “allergic to pencillin” label, and their parents vaguely remember that he received amoxicillin for a “respiratory infection” at the age of 2 and several days after that developed a rash, the chances of him having a true allergy to penicillin is very low.

Is penicillin allergy hereditary?

No. So far a significant genetic component related to penicillin allergy has not been found.
This is an important question that I often encounter at the office – a mother will remember being allergic to penicillin and would rather avoid giving her child penicillin for concern that they are allergic, as well. It is worth noting that there aren’t any guidelines for the avoidance of penicillin when one or both parents are allergic to the drugs.

Are there different types of allergic reactions to medications?

Yes. And the differences are very important as not every reaction to a drug is considered an allergy.
Side effect – when we take a medication we obviously hope to get its best and most desired effects. Unfortunately, sometimes, unwanted effects of the drug occur. The general name for this is “side effects” or “adverse effects”. Most of the adverse effects are non-allergic – for example if a child who was taking amoxicillin-clavulanate develops abdominal pain and diarrhea the following day – then this is a common and excepted side effect of the drug. But this does not mean the child is allergic to the drug.
Hypersensitivity – within the large group of effects due to side effects, there is a smaller group of reactions that occur in a small portion of the population. Or in other words, most people will not suffer from these, but some specific children may. For example, for patients with G6PD deficiency, taking certain medications can cause destruction of red blood cells, but other patients who do not have this deficiency will not experience this. This type of reaction is not considered an allergic reaction either.

What does it mean to have a “true” allergic reaction to penicillin?

Allergic reactions are considered “hypersensitivity” reactions. These entail overactivation of the immune system following exposure to the drug. What happens when a child has an allergic reaction to a drug? When the drug is taken, the immune system identifies the drug or its products as a substance that the body must attack, and that is when unwanted effects develop.
Practically speaking, it is important to divide these types of reactions into:
IgE mediated reactions – the main characteristics of these types of reactions are how dangerous they are and how quickly they develop from the moment the medication is taken to the time the reaction appears. These are the type of reactions that come to mind when we think of allergies and they include swelling of the lips, shortness of breath, certain rashes, abdominal pain, vomiting and other life-threatening events that are referred to as anaphylaxis (find out more here).
There are non-IgE mediated effects – these are more variable in their behaviour, but are characterized by a late onset after exposure. The most common effect is a rash that presents several days after exposure to the drug.
There are other severe reactions that are mediated by the immune system but are non-IgE, but they are rare and we will not be getting into them in this chapter.

How can one diagnose allergies to penicillin or penicillin sensitivity?

First of all, the history is very important. When signs and symptoms develop as soon as exposure occurs, respiratory symptoms as well as anaphylactic reactions – these are more likely to point towards IgE-mediated reactions that are dangerous.
Nonspecific symptoms such as abdominal pain, headaches or simply a family history of allergy to penicillin reduce the likelihood of there being a true allergy to penicillin.
Since most of the time a rash will be reported, it is a good idea to take a picture of the rash from several different angles and at several different times. Your doctor will want to know the characteristic of the rash and its timing, whether there was exposure before or after to a different medication from the same family, and whether the reaction was treated and the what the effect of the treatment was.
Practically speaking, when the symptoms appear, it is hard to distinguish between skin reactions that developed as a result of penicillin and those that developed because of the actual infection, and that is why sometimes the child will be labelled as “suspected to have penicillin allergy” and will have to avoid penicillin until the investigation is completed. As you will see below, it is important to complete the investigations in order to confirm or rule out the suspected allergy.
The decision on how to proceed with investigation depends on many different variables, including the time of onset and the important of the antibiotic treatment for the specific patient. The decision is left to the discretion of the allergic disease specialist.

What kind of allergic tests can be performed at the allergic disease specialist’s office?

The diagnostic toolbox includes skin tests that can be helpful in confirming or ruling out the suspicion. In addition, the final test is a drug challenge test.
What is a drug challenge test? Practically speaking, it means taking the drug under medical supervision, usually at an allergy clinic in a hospital, and ruling out allergy if there are no signs of reaction within 2 hours. Usually, since the suspicion for allergy is low, one can complete a challenge test without having done the skin tests prior to that.
If the suspicion is high and the patient had a very severe reaction after exposure, the risks implicated in a challenge test do not outweigh the benefits and these patients are forced to keep the allergy label.

Why is it so important to get rid of that allergy label?

Contrary to food allergy, medications are generally not something you are accidentally exposed to, and therefore if someone has an allergy to a rare medication that is not so important to them, the management would simply be to avoid that medication and get on with their life.
Penicillin on the other hand, is a very commonly prescribed medication and having to avoid it can sometimes lead to having to use alternatives that are not as good and not as suitable. These alternative medications can lead to side effects and to therapy with antibiotics that are very broad spectrum, even when that is not necessarily needed, and that may lead to the development of resistant bacteria and even prolongation of hospitalization for the purpose of treatment with intravenous medications if a simpler option doesn’t exist.
An important point to keep in mind – if you find out that your child is not allergic to penicillin following a full investigation, it is important to make sure that label comes off their medical charts at their family doctor’s or pediatrician’s, to avoid any future confusion.

What about other antibiotics such as cephalexin and cefixime?

Cefixime is another commonly used antibiotic in children and it belongs to the cephalosporin family, it is a distant relative of the penicillin family. In the past it was thought that if someone has penicillin allergy then they should also avoid cephalosporins. Nowadays we know that most patients who developed a rash after being exposed to penicillin, in the context of an infectious disease, can safely receive cephalosporins. In cases of severe penicillin allergy, because of the small chance of cross-reaction between the two medications, it is best to consult with your pediatrician or your pediatric allergic disease specialist when administering cephalosporins. That same type of consult is warranted when a child who had developed an allergic reaction to cefixime needs to take amoxicillin.
Therefore, when in doubt, simply consult your pediatrician or pediatric allergic disease specialist.

What about azithromycin?

Azithromycin is a completely different medication and it is often the best available alternative to amoxicillin when a patient is found to have a true, IgE mediated allergy to amoxicillin.

I have been worked up and found to be truly allergic to amoxicillin – what now?

Do not take any medications belonging to the penicillin family as they can be very dangerous for you. Whenever you start a new medication, make sure to let your caretaker know that you are allergic to penicillin.
Patients who have a history of severe reaction should find out, together with the help of their doctor, whether they can take cephalosporins, which are a family of drugs that are similar to penicillins, in order to try and broaden the options available at times of infections.
It’s worth noting that cephalosporins and its derivatives are also available in intravenous forms, therefore prior to starting medications at the hospital or urgent care clinics, it is important to let your caretaker know about your allergies, so that they are aware and choose the right drug for you.

In summary, if your child has been previously labelled with “penicillin allergy” or “amoxicillin allergy”, the chance that they are truly allergic to drugs belonging to this family is quite low. It is a good idea to consult with a specialist and to try and get rid of that label in order to make things easier for yourself and for them during times of childhood diseases and later in adulthood, in relation to antibiotic treatment, whenever it may be needed.
Good luck!