All You Need To Know About Penicillin Allergy

Many people report being allergic to penicillin. There are many side effects to this antibiotic that are not allergic in nature. Most people who report having this reaction are not allergic in the classic sense. Their reactions are not immune induced.

But those that do experience a type I hypersensitivity reaction are some of the most severe reactions to penicillin experienced and can be life threatening.


Type I Penicillin Hypersensitivity Reactions

The Beta Lactam ring is a segment on the penicillin molecule that is important for it’s function. It is how this drug works, by preventing the bacteria to replicate. The beta lactam ring is also the site where antibiotic resistance develops and is the site that stimulates type I allergic reactions.

Susceptible people inherit this drug allergy. The beta lactam ring stimulates the production of antibody’s that attach themselves onto mast cell walls. When the next exposure to penicillin occurs, these antibodies immediately force the mass cells to release their contents which are histamine, cytokines and other compounds associated with allergic reactions.

With each subsequent exposure, more antibodies attach to more mast cells. When a critical mass is reached and exposure occurs, life threatening amounts of histamine and associated biochemicals can flood the body. This is called anaphylaxis when a severe, life threatening allergic reaction occurs.

10% of the population reports a penicillin allergy but estimates are that only 1% are truly are allergic. Of those 0.01% will develop anaphylaxis. There seems to be a genetic link with a preponderance noted in families.



Most people progress through a long course of slowly worsening reactions and symptoms, however; it can also be quite rapid. Anaphylaxis doesn’t occur on the first exposure, it can take two or three or a hundred to reach the critical level required.

Symptoms associated with penicillin allergy include:

  • Urticaria (hives)
  • Pruritus (itching)
  • Angioedema (swelling hands, feet, lips, eyelids, tongue or lips)
  • Wheezing/shortness of breath (may sometimes be dry cough)
  • Tightness in throat
  • Tachycardia (rapid heart rate)
  • Feeling of impending doom


Severe Allergic Reactions/Rashes

Skin rash as result of penicillin allergy

Skin rash as result of penicillin allergy

Several uncommon but severe reactions can develop.

Anaphylaxis Purpura also called Henock-Schonlein Purpura is a vasculitis; an inflammation of blood vessels that causes black and blue lesions and other symptoms including joint aches and fever.

Stevens-Johnson Syndrome and Erythema Multiforme are two severe uncommon reactions to many viruses, bacteria’s and medications including penicillins. They can be life threatening and often present large circinate (irregular round) bull’s eye or target lesions.


Other Penicillin Rashes

One common reason people are diagnosed with penicillin allergy is from a viral exanthum. Several viruses develop an exanthum, a fine red skin reaction as part of the syndrome. Typically it occurs after several days of illness. The patient goes to the doctor and is given an antibiotic. When the exanthum develops after initiating antibiotics it is labeled an allergic reaction.

There are some viral and antibiotic combination reactions that are not immune mediated. For example certain people will develop a red skin rash from amoxicillin taken in mononucleosis (Epstein Barr virus). Again this is not an allergy but is often labeled as such.


Other Beta Lactam Antibiotics

Penicillin shares the beta lactam ring configuration with other antibiotics specifically cephlosporins, monobactams and carbapenems. Recent investigation suggests that it is a certain position of the molecule, not the molecule itself that is responsible for the reaction. Even though there appears to be little or no risk associated with the beta lactam ring in other antibiotics, they are still not recommended for those with severe or rapidly progressive reactions to penicillin.



Severe type I hypersensitivity reactions are in general dealt with using adrenalin (epinephrine), antihistamine, usually both an H1 blocker like Benadryl and H2 blocker like cimetidine, and intravenous steroids. Patients are typically sent home on antihistamines and decreasing doses of oral steroids.

Steroids in acute allergic reactions provide two functions. They tie up the cells creating the immediate threat. They also modulate production of the immunoglobulins to minimize the progression of the response for the next time.

People with severe or rapidly progressive allergic reactions to this or any drug should wear identification of such to alert health care professionals in an emergency. Epi pens (self-injectable adrenalin for allergic emergencies) are generally not indicated as the risk of random penicillin exposure in the environment is minimal. If occupational risks are present, pharmacist or nurse for example, it may be prudent to keep one close by.


Allergy Testing

If a clinical condition requires penicillin treatment in a patient with suspected allergy a skin test can be performed. A small amount of the drug is injected just under the first layer of skin. If a local inflammatory reaction occurs at the sire of injection the patient if allergic. This is called a wheal and flare. Serum testing can be done but results are not as specific and have been considered unreliable.


Penicillin allergy can present a dilemma for health care professionals and patients. With many therapeutic choices, it seldom becomes a treatment issue. In emergency situations it can pose a concern but is usually easily managed.

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