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Penicillin Allergy: Symptoms, Testing, and Treatment Strategies

Written by Andrew Le, MD

UpdatedFebruary 29, 2024

Relying on assumptions about allergies to medications can have serious consequences. It may result in unnecessary precautions being taken in future medical scenarios, potentially leading to limited treatment options.

Among the most misunderstood is the penicillin allergy. Surprisingly, 10% of the US population believes they're allergic to penicillin. However, only less than 1% are truly allergic.

By thoroughly understanding penicillin allergy, we can guarantee that individuals receive the precise treatment they need. This knowledge will help us to actively contribute to reducing the use of alternative, and potentially less effective medications.

🔑 Key Takeaways

  • Penicillin, discovered by Alexander Fleming, is a widely used antibiotic but is also a commonly reported allergy.
  • Gastrointestinal symptoms like nausea and vomiting can occur, especially with oral administration of penicillin.
  • Delayed reactions can surface 1 to 2 weeks after penicillin exposure and include joint pain, rash, and fatigue.
  • It's crucial to differentiate between allergic reactions and side effects for proper medical management.
  • True penicillin allergies are reported by less than 1% of the US population, despite 10% claiming the allergy.
  • Individuals allergic to one type of penicillin should exercise caution with other penicillin variants.
  • Cephalosporins lacking the ß-lactam side chain are considered safe alternatives for penicillin-allergic individuals.

Understanding Penicillin Allergy

Discovered by Alexander Fleming in 1928, penicillin (PCN) gained widespread usage in 1942 for effectively treating staphylococcal and streptococcal bacterial infections. Today, penicillin is still a widely prescribed and effective antibiotic in healthcare. Yet, penicillin allergy is a commonly reported concern.

A penicillin allergy is an adverse reaction that occurs when the body's immune system mistakenly identifies penicillin or related antibiotics as harmful substances. In individuals with this allergy, the immune system produces antibodies, known as immunoglobulin E (IgE), in response to penicillin. Upon subsequent exposure, these antibodies trigger the release of histamines and other chemicals, leading to allergic symptoms.

Symptoms of Penicillin Allergy

The symptoms of a penicillin allergy may vary from mild discomfort to severe, potentially life-threatening complications. Here are some of the common symptoms associated with penicillin allergies.

Immediate Onset Symptoms

Immediate reactions can happen within 20 minutes to 1 hour after administration. Skin manifestations are often the first and most common finding of a penicillin allergy. However, they are absent in 10% to 20% of patients experiencing the allergic reaction. Common skin symptoms are:

  • Hives or urticaria
  • Reddening of the face, neck, or upper chest (flushing)
  • Itchy skin
  • Swelling under the skin, also called angioedema

Although the incidence of anaphylactic reactions due to penicillin only ranges from 0.02% to 0.04%, immediate reactions may exhibit signs and symptoms typical of acute anaphylaxis. These include:

  • Shortness of breath (Dyspnea)
  • Wheezing
  • Coughing
  • Low blood pressure (Hypotension)
  • Fast heartbeat (Tachycardia)
  • Mental status change
  • Gastrointestinal (GI) Symptoms

💡 Did You Know?

GI symptoms, such as nausea, vomiting, and sore mouth, are reported in over 1% of patients, especially with oral administration.

Delayed Onset Symptoms

In some instances, allergic reactions may surface within 1 to 2 weeks following penicillin exposure. These delayed symptoms can include:

Delayed reactions involve a different part of our immune system. When these components become active, they trigger a series of responses, leading to various types of hypersensitivity reactions.

These reactions can be quite serious and result in conditions like:

  • Hemolytic Anemia: This is a condition where the body rapidly breaks down red blood cells at a rate faster than it can produce them. This can result in symptoms such as fatigue, paleness, and jaundice.
  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A severe and potentially life-threatening reaction to certain medications. It's characterized by a widespread skin rash, fever, inflammation of internal organs, and an increase in a type of white blood cell called eosinophils.
  • Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): These are severe skin conditions characterized by widespread blistering and shedding of the skin's top layer.
  • Vasculitis: A medical condition characterized by inflammation of the blood vessels. This inflammation can restrict blood flow and cause various symptoms depending on which organs and tissues are affected.
  • Interstitial Nephritis: Involves inflammation of the tissue surrounding the kidney's tubules. This inflammation can lead to problems with kidney function.
  • Thrombocytopenia: Characterized by a lower-than-normal number of platelets in the blood. This can lead to bleeding and easy bruising.
  • Neutropenia: A medical condition characterized by a lower-than-normal level of neutrophils, a type of white blood cell crucial for fighting infections. When someone has neutropenia, they may be more susceptible to infections.

🧠 Knowledge Check

SJS and TEN belong to a similar disease category. The key distinction lies in the extent of skin involvement. When epidermal detachment affects less than 10% of the body surface area, it is categorized as SJS.

Now that we've explored the various symptoms associated with a penicillin allergy, it's important to distinguish an allergic reaction from a mere side effect. Understanding this difference is crucial for effective medical management and ensuring patient safety.

Differentiating Between An Allergic Reaction And Side Effects

Knowing whether the symptoms are due to an allergy or a side effect helps healthcare providers choose the right course of action. Doctors sometimes choose broad-spectrum antibiotics as an alternative to penicillins. However, using broad-spectrum antibiotics can raise healthcare expenses and the risk of antibiotic resistance.

The Centers for Disease Control and Prevention (CDC) reports approximately 47 million unnecessary antibiotic courses are prescribed annually in US medical facilities, making up around 30% of all prescriptions.

To help you understand this issue, it's important to remember penicillin's side effects. These are:

📕 Definition:

A broad-spectrum antibiotic is a type of antibiotic that is effective against a wide range of bacteria, both Gram-positive and Gram-negative. It is capable of targeting a diverse array of bacterial species. In contrast, penicillin is a more specific antibiotic that primarily targets Gram-positive bacteria.

Cross-Reactivity with Other Antibiotics

Individuals who have experienced allergic reactions to one type of penicillin should exercise caution with other penicillin variants. Until recently, it was widely accepted that there was up to a 10% cross-sensitivity between penicillin-derivatives, and the non-penicillin cephalosporins, and carbapenems, which share a similar ß-lactam ring structure.

The different types of penicillin include:

  • Amoxicillin
  • Ampicillin
  • Carbenicillin
  • Dicloxacillin
  • Nafcillin
  • Oxacillin
  • Penicillin G
  • Penicillin V
  • Piperacillin
  • Ticarcillin

For individuals with penicillin allergies, certain cephalosporins bear a higher risk of cross-reactivity due to their similar side chains:

  • Cephalexin
  • Cefadroxil
  • Ceflaclor
  • Cephradine
  • Cefprozil
  • Ceftriaxone
  • Cefpodoxime

Recent studies have shown a crucial insight into the immunological response. Rather than the shared ß-lactam structure, the major determinant in allergic reactions lies in the similarity between the side chain of first-generation cephalosporins and penicillins.

Cephalosporins lacking the ß-lactam side chain are considered safe and can be used as alternative antibiotics for people with penicillin allergy. These include:

  • Cefazolin
  • Cefuroxime
  • Cefdinir
  • Cefixime
  • Ceftibuten

This discovery holds significant implications for those with established IgE-mediated penicillin allergies.

Diagnosing Penicillin Allergy

To diagnose a penicillin allergy, healthcare providers meticulously review a patient's medical history. This includes a thorough examination of any previous allergic reactions and inquiries about related medications taken in the past, such as amoxicillin or cephalosporins.

Several penicillin allergy tests are available, each varying in accuracy and method of administration. Here are the main options:

Skin Prick Test

Penicillin skin testing is the primary validated method in the US. This procedure involves a controlled skin-prick test where both major and minor penicillin determinants and control are applied.

After 15 minutes, the area is examined. A positive result is indicated by the development of a wheal of at least 3 mm in diameter, accompanied by erythema. This test should not be performed if the initial reaction to penicillin was a severe non-IgE mediated reaction.

Intradermal Testing

If penicillin skin testing yields negative results, intradermal testing using the same antigenic determinants can be considered. Similar to skin testing, a positive intradermal test is characterized by developing a wheal and erythema of 3 mm or more at the injection site.

Readings are taken at 15 minutes for immediate reactions and at 48 and 72 hours for delayed reactions. Patients may need to wait up to 6 weeks after initial testing before undergoing intradermal testing.

Oral Drug Test

A graded-dose challenge may be administered when skin testing is inconclusive. This involves gradually administering increasing doses of penicillin, starting with 1/100 of the dose if the initial reaction was anaphylactic.

Each dose is followed by a 30 to 60-minute observation period. If no adverse reaction occurs, the patient receives a full dose, followed by further observation. This testing is conducted at least 4 to 6 weeks after any acute reaction, steroid or antihistamine use, or signs of asthma or urticaria.

✅ Pro Tip

If you're scheduling an appointment with an allergist, it's important to ensure they hold certification from the American Board of Allergy and Immunology as a board-certified specialist. You can easily check your doctor's certification status by visiting Certification Matters and entering their name.

These measures ensure patients receive safe and effective infection treatment while avoiding potential allergic reactions. Consulting with a qualified healthcare provider is paramount in navigating this diagnostic process.

Management and Treatment of a Penicillin Allergy

A range of treatments are available for penicillin allergies, each tailored to the severity of the reaction and the specific needs of the individual.

The options below are designed to address allergic symptoms after they occur.

1. Antihistamines

Antihistamines come in various forms, including oral tablets, liquids, creams, and gels. Over-the-counter options include:

  • Diphenhydramine (commonly known as Benadryl)
  • Cetirizine (marketed as Zyrtec)
  • Loratadine (sold as Claritin)

2. Corticosteroids

For more severe penicillin allergy reactions involving inflammation, corticosteroids are often prescribed. These medications can be administered orally or via injection, typically for short-term use.

Examples of corticosteroids include:

  • Prednisone
  • Methylprednisolone
  • Hydrocortisone

3. Immunotherapy (Desensitization)

Immunotherapy, also known as desensitization, is a specialized treatment approach that aims to increase a patient's tolerance to penicillin. This is done through a carefully supervised process of gradually administering increasing doses of penicillin.

4. Epinephrine Injections

In severe allergic reactions, including anaphylaxis, epinephrine injections play a critical role. EpiPens are designed to be administered promptly, swiftly reversing symptoms like breathing difficulties and swelling.

❗ Important Note

Immediate medical attention is essential even after administering epinephrine. Remember, epinephrine is not a cure for a severe allergic reaction, but rather a life-saving measure to buy time for further medical treatment.

These options provide valuable relief, ensuring that individuals can effectively manage their penicillin allergies while minimizing the risk of severe reactions.

Preventing Penicillin Allergy Reactions

The most straightforward preventive measure for individuals with a known penicillin allergy is to steer clear of the penicillin drug class altogether. Here are some essential steps you can take to safeguard your well-being:

  • Notify Healthcare Providers: Ensure that your penicillin allergy, or any other antibiotic allergy, is prominently documented in your medical record. This information should be readily accessible to all healthcare professionals involved in your care, including specialists and even your dentist.
  • Utilize a Medical Alert Bracelet: Wearing a medical alert bracelet that explicitly states your drug allergy can be a lifesaver in emergency situations. This simple accessory provides crucial information to healthcare providers, ensuring they administer appropriate treatment promptly.

Source: AAAAI

Taking these precautionary measures will help you confidently promote safety, ensuring that any prescribed medications align with your specific needs and allergy profile.

The Bottom Line

Recognizing the symptoms, both immediate and delayed onset, allows for timely intervention. It's essential to differentiate between allergic reactions and non-allergic side effects like upset stomach or diarrhea to make informed medical decisions.

Diagnosing penicillin allergy can be achieved through various tests, including skin prick tests, intradermal testing, and oral drug tests. In terms of management and treatment, options range from antihistamines and corticosteroids for milder cases to immunotherapy (desensitization) and epinephrine injections for more severe reactions.

For individuals with confirmed penicillin allergies, wearing a medical alert bracelet and discussing suitable alternatives are essential steps in ensuring safe and effective medical care. Remember, being well-informed about our health is a fundamental aspect of responsible self-care.

FAQs on Penicillin Allergy

Can a penicillin allergy develop later in life?

Yes, it's possible for a penicillin allergy to emerge at any point, even if you've taken it before without issues. Allergic reactions can manifest upon subsequent exposure.

What should I do if I suspect a penicillin allergy?

If you suspect a penicillin allergy, consult a healthcare professional. They can conduct tests to confirm the allergy and suggest suitable alternative antibiotics.

Is penicillin allergy hereditary?

While there may be a genetic predisposition to allergies, a penicillin allergy is not directly inherited. However, a family history of allergies might increase the likelihood of developing one.

Is it safe to receive a COVID-19 vaccine with a penicillin allergy?

Having a penicillin allergy is not a contraindication for receiving the COVID-19 vaccine. Consult your healthcare provider for specific guidance based on your medical history.

How can I prevent accidental exposure to penicillin?

Inform all healthcare providers about your penicillin allergy, wear a medical alert bracelet, and keep a record of your allergy readily available. This will ensure you receive alternative antibiotics if needed.