Penicillin-family Drug Allergy Evaluation and Testing

It can be difficult to know whether or not a reaction to a penicillin- related medication indicates a true allergy. An evaluation and some testing can help


Approximately 10% of people report that they are allergic to a penicillin-family medication. However, greater than 90% of those who believe they are allergic to a penicillin-class drug are not actually allergic. In fact, most reactions that occur while taking a penicillin-class drug are not an allergy. Either they are a non-IgE related (meaning non-allergy related) immune response, a medication side effect, or actually related to the underlying infection. For example, if you have a vague history of a rash when you were young and on a penicillin or related medicine, you are very likely not actually allergic. There is also no clear inheritance pattern to penicillin drug allergies, so avoiding these medicines because a family member is allergic is generally not necessary.

For the small percentage of people who are truly allergic, it is very important to know exactly which medications in the penicillin and broader “beta-lactam” family of drugs you need to avoid. Interestingly, many people who have a true penicillin-family drug allergy will lose their allergy after a period of time, and it does not often come back.

Finding out whether or not you (or your child) currently have a true penicillin-class drug allergy has important benefits to both you personally and our community as a whole. The complete evaluation at our clinic involves a detailed history, likely allergen skin testing and/or blood IgE testing, and then possibly a drug challenge on another day. If you are labeled as penicillin allergic, when you need a penicillin-class antibiotic for an infection, a broad-spectrum antibiotic will be used instead (which kills a much larger array of bacteria than is needed to heal your infection). These antibiotics often have much worse and more frequent side effects for you than the penicillin-class drugs, and their overuse contributes to the growth and spread of antibiotic-resistant bacteria in the community (bacteria that cause severe infections that we currently have no way at all to treat). A proper evaluation can help you understand if you can take penicillin-class antibiotics when needed or if you truly need to avoid them.

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Many reactions that occur while taking a penicillin-class drug are not an allergy (IgE-mediated)

It is important to try to distinguish between a penicillin drug allergy (which can lead to a potentially severe allergic reaction) and a different, much less dangerous type of penicillin effect. True penicillin allergy typically doesn’t occur the first time you have ever taken the medicine. It generally occurs on a subsequent exposure, typically within 30 minutes of your first or second dose of that treatment course, and can include hives (raised, pink, itchy and swollen bumps that move around to different places on the body), breathing problems, severe vomiting, dizziness or passing out, or any combination of allergy or anaphylaxis symptoms. Anaphylaxis from penicillin-class medications is rare overall but does occur – more likely from an IV penicillin-class medication than an oral pill.

Much more common than a true penicillin allergy is a non-IgE related immune response (meaning non-allergic immune response) to the drug, a side effect from the drug, or a reaction related to the underlying infection being treated with the drug. For example, a rash that consists of flat or slightly raised pink bumps that occur on the chest, abdomen, and back, and sometimes also the extremities and face is a very common occurrence while on penicillin-class medications. This rash is seen frequently in young children with an ear infection who are being treated with amoxicillin for the first time or second time. Often, it is actually more beneficial to continue on treatment with the antibiotic for the infection, and stopping the antibiotic does not make the rash go away. This rash is not due to drug allergen and IgE antibodies activating the allergy pathway, and it does not pose a significant health risk. It can have various causes – like other non-allergy antibodies (like IgG) being produced to a component of the drug, or simply the underlying infection (not the medication at all). This rash can look bad but is generally not itchy or painful and doesn’t appear to specifically bother the person who has it. One way to potentially distinguish it from an allergic reaction is timing – it typically starts 5-10 days into a person’s first course of treatment (but can start a little bit earlier if it occurs in a subsequent course of treatment), and it can last for days to a few weeks. Unlike with true drug allergy, this rash is not likely to recur with a future course of treatment with the same or another penicillin-class medication.

Penicillin-family antibiotics also can cause GI side effects like stomach aches, nausea, and diarrhea. These are typically not IgE-mediated (allergic) reactions either and are fairly common. If you have any type of reaction that you feel may be due to a medication, it is important to talk to your doctor or allergist directly about the details so that whether or not you have an allergy to the medication can be properly determined.

There is no clear inheritance pattern for penicillin allergy, so you are probably not allergic to penicillin-class medications even if a family member is)

It is common for us to hear that someone is avoiding penicillin-class medications because they think they are allergic since another family member is reportedly allergic. However, most of the time, that person has absolutely no need to avoid penicillin-class of medications if one of them is appropriate for a treatment. The genetics of penicillin allergy have been widely studied, and there is no consistent inheritance pattern for penicillin allergy. This makes it difficult to currently use the information that a family member is allergic to penicillin to in any way predict what that may mean for you.

Allergies to a specific allergen do not appear to be strongly genetic. However, there does seem to be a propensity towards allergic diseases (eczema, hayfever, asthma, etc) clustering in families, with some families having many members with various allergic conditions, and other families having very few to none. This does suggest some genetic component(s) promoting an allergic phenotype amongst family members, but genetic links between passing on a specific allergy from parent to child, such as penicillin allergy, have not been established. There are occasionally specific allergen correlations noticed in family members, like an increased risk of peanut allergy in the sibling of someone allergic to peanuts compared to the general population, so it is important to remember that we do not fully know the extent of the role of genetics in allergy as of yet. However, it is likely that the genetics of allergic disease, including drug allergy, is very complex and nuanced with incredible variation much like so many other immune-related topics.

Over-reporting of penicillin-class drug allergy is leading to more medication adverse effects and the growth of antibiotic-resistant bacteria

The 2 most common scenarios noted by someone who reports a penicillin allergy is that they were either 1) told that they had a rash to penicillin or amoxicillin when they were young or 2) have a family member who is “allergic” to penicillin. Fortunately, the large majority of these patients are not actually allergic to these medications and could take this class of medication when needed without significant issue. Unfortunately, the current system does not automatically help you validate any potential medication allergies you report unless you specifically request or seek out the proper evaluation.

When a person reports a possible penicillin-family drug allergy, they are often labeled as “penicillin-family allergic” without a specific evaluation to determine whether or not this is actually true or not. Then, whenever a penicillin or related antibiotic is needed to treat an infection you have, your provider will see the allergy label and skip the whole penicillin-family of medications (and sometimes even the entire beta-lactam class) in order to keep you safe from your reported allergy. A “broad-spectrum” antibiotic will be used instead because it kills a wide array of bacteria and the hope is that amidst that it will also kill the type bacteria causing your infection.  These broad-spectrum antibiotics unfortunately also come with more risky potential side effects (such as risk of tendon rupture, muscle or joint issues, sun sensitivity, confusion, insomnia, hallucinations, severe diarrhea and gut health imbalance, risk of subsequent GI infection, and more). And the more that these broad-spectrum antibiotics are used in our community as a whole, the more that antibiotic-resistant bacteria (those that cannot be killed by any of our current medications) are left unchecked by other bacteria, giving them free reign to feed and reproduce and spread, potentially causing devastating and untreatable infections.

Allergenuity Health offers a thorough assessment for those with a possible penicillin-family drug allergy

It is one of our goals to educate you on this important personal and community health issue and offer a proper evaluation to anyone in this situation.

Some of the most important pieces of information Dr. Schroeder will gather from you during a penicillin allergy evaluation with us include: which penicillin-family medication were you (or your child) taking when the reaction occurred, was it your first time taking this medication or any penicillin-class medication, after which dose did you have a reaction, how quickly after the dose did your reaction begin, what were the details of the reaction, and how many years ago did this occur? In many cases, providing this type of detailed information can give a trained allergist a fairly clear idea of whether or not it is likely that you had an allergic reaction, experienced an adverse effect of the medication, or experienced symptoms most likely related to your illness at that time.

Another interesting and nice fact is that even if you did have an allergic reaction to the medication in the past, with enough passage of time and lack of exposure, it has been shown that many previously penicillin-allergic patients appear to completely lose their allergy.

To get further information if needed, blood serum IgE tests and/or allergen skin tests to penicillin-class medications and important components of these drugs can be performed. Not every clinic performs this testing the same way or with the same components, so you may want to ask for details about the available testing before choosing where to have your evaluation performed. At Allergenuity Health, we are working with several quality vendors and labs to make sure that collectively we can obtain the known important penicillin-class components in order to provide you with as accurate a diagnosis as possible. The process for penicillin-family allergen skin testing includes some stages, starting with dilutions (weaker versions of the allergens) first if needed to keep safe depending on your clinical history and other factors. Both skin prick testing and subsequent intradermal testing may be performed to the extent needed in order to help come to a more clear diagnosis.

A drug challenge procedure may be performed as the final step of the evaluation (on a separate occasion) to further confirm that you are not allergic and that it is safe for you to use penicillin or amoxicillin etc

If your clinical history and testing suggest that you either were never allergic or may no longer be allergic, it is often beneficial to further attempt to confirm this by seeing how your body reacts to a dose of the medication when you are not sick. This is called a medication or drug challenge test and is done in the clinic for your safety. You would take one dose of the appropriate medication and then be observed for at least 2 hours so that we can monitor both you and your vital signs for any early clues suggestive of an allergic reaction. In the unlikely event that you do have a reaction, your symptoms will be treated promptly and you will be further monitored. When appropriate, Dr. Schroeder will review with you what your history and testing suggest about penicillin-class drug allergy and what precautions to take. If no reaction occurs during the drug challenge, Dr. Schroeder will put all the pieces of the story together and tell you what she believes is your current allergic status and the likelihood of these medications being safe for you to use if needed in the future.

It is generally recommended that you avoid all medications in the immediate Penicillin Family if you are truly penicillin allergic due to cross-reactivity, and you may or may not need to avoid some related Cephalosporin antibiotics depending on the features of your specific allergy

The immediate penicillin family typically includes penicillin, amoxicillin, amoxicillin-clavulanate (Augmentin), ampicillin, dicloxacillin, nafcillin, and piperacillin-tazobactam (Zosyn). Some penicillin-allergic individuals will also need to avoid some or all medications in the cephalosporin class as well (considered a cousin of the penicillin class). We will be able to advise you more specifically after your evaluation depending on your history and the specific results of your component testing.

If you are truly allergic to penicillin and have an infection where ONLY a penicillin will work, it may be possible to undergo penicillin treatment by using a desensitization procedure

A penicillin drug desensitization procedure is typically performed in a hospital setting for your safety (especially for IV medications) under the guidance of an allergist there, so this desensitization procedure would not be performed at our clinic by Dr. Schroeder. However, we want you to know about it because the typical penicillin-class drug desensitization process has had excellent success for patients who need it and there are studied and published protocols. Typically, a dose of the drug is given by mouth or intravenously every 15-20 minutes over 4 or more hours under strict monitoring. Once the desired dose has been achieved and tolerated, most people can continue to be treated with penicillin normally until the end of their treatment course. A desensitization procedure provides temporary tolerance to your allergen, so once the treatment course is finished, your penicillin-allergic status likely returns. Therefore, you would be advised to continue to avoid penicillin and cross-reactive medications again, and if you ever needed penicillin treatment in the future, it would be advisable to undergo a repeat desensitization procedure.

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