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Patient education: Significance of negative penicillin allergy skin testing (Beyond the Basics)

Roland Solensky, MD
Section Editor
N Franklin Adkinson, Jr, MD
Deputy Editor
Anna M Feldweg, MD
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Penicillin skin testing is a way to test a person for an allergy to penicillin. Penicillin is an antibiotic commonly used to treat bacterial infections. There are many different penicillins, including amoxicillin, nafcillin, ampicillin, and others. The skin is pricked or injected with solutions containing penicillin and observed for a reaction. The test is considered positive if an itchy, red bump at the site of the skin test appears in 15 to 20 minutes and negative if nothing happens. Skin testing is usually done in an allergist's office or hospital. (See "Patient education: Allergy to penicillin and related antibiotics (Beyond the Basics)", section on 'Penicillin allergy testing'.)


Penicillin skin testing is performed in people who have had a possible "immediate-type" allergic reaction to penicillin or a related antibiotic. Immediate-type reactions are allergic reactions that usually begin within a few minutes to one hour after taking the medicine. These reactions can be serious or even fatal, although most are not. (See "Patient education: Allergy to penicillin and related antibiotics (Beyond the Basics)", section on 'Allergic reactions'.)

Symptoms of immediate-type reactions can include:

Skin – Itching, flushing, hives (urticaria) (picture 1), swelling (angioedema)

Eyes – Itching, tearing, redness, swelling of the skin around the eyes

Nose and mouth – Sneezing, runny nose, nasal congestion, swelling of the tongue (picture 2), metallic taste

Lungs and throat – Difficulty getting air in or out, repeated coughing, chest tightness, wheezing or other sounds of labored breathing, increased mucus production, swelling or itching in the throat, hoarseness, change in voice, sensation of choking

Heart and circulation – Dizziness, weakness, fainting, an irregular (or fast or slow) heart rate, low blood pressure

Digestive system – Nausea, vomiting, abdominal cramps, diarrhea (occurring suddenly soon after taking the medicine)

Nervous system – Anxiety, confusion, sense of impending doom

Penicillin skin testing is also performed when the history of prior reaction is not clear; for example, if the person got a rash while taking penicillin in the past, but may or may not have had an immediate-type reaction.

Penicillin skin testing tells your allergist if you make a specific type of allergic antibody that recognizes penicillin or the chemicals penicillin changes into as it is broken down by the body. The antibody is called "immunoglobulin E" or "IgE." If IgE recognizing penicillin is present in your body, it means that there is a risk that you could have a serious immediate-type allergic reaction to penicillin or related antibiotics if you take them again in the future.


If you had skin testing and it was negative, meaning that there was no reaction on the skin, then you are very unlikely to have the allergic antibody in your system. However, because the testing is not 100 percent reliable, most allergists take the extra step of giving a single dose of penicillin (or a related antibiotic) under medical observation. This is to make sure you do not have a reaction after actually taking the medicine. Also, other health care providers who treat you in the future are much more likely to prescribe penicillin if you can tell them that you have received (and tolerated) a dose.

If your penicillin skin test was negative, and you took a dose of penicillin under medical observation without a reaction, then it is extremely unlikely that you will have an immediate-type allergic reaction if you take penicillin in the future.


Having a negative penicillin skin test does not mean that you will never react to penicillin (or related antibiotics) in the future. Skin testing only gives information about immediate-type reactions. You could still have other types of reactions, which are unrelated to immediate-type reactions (see 'Other reactions to penicillin' below). There is no reliable way to predict other types of allergic reactions.

Other reactions to penicillin — There are several other types of penicillin reactions that are not caused by the immunoglobulin E (IgE) antibody and cannot be predicted by a skin test. The most common is a rash. Some people seem to be more prone than others to developing mild rashes while taking antibiotics for reasons that are not understood.

Rashes from penicillin usually appear after several days of penicillin therapy. They occur about 2 percent of the time for most penicillins, but more frequently for some penicillins like amoxicillin. The rash may last for days to weeks and may or may not be itchy. This can be annoying, but is rarely dangerous. If you develop a rash during or just after a course of penicillin in the future, call your health care provider for advice about what to do. Sometimes you can treat the rash and finish the penicillin course, and sometimes it is better to stop the penicillin right away. If you can, take a picture of the rash before you treat it, because this will help providers who take care of you in the future.

There are other more serious allergic reactions that may happen despite negative penicillin skin testing. Fortunately, these are rare. Symptoms of serious reactions include:


Flu-like symptoms (fatigue, muscle or joint aches)

Swelling of the face or hands

Sensitivity to light (eye pain when looking at bright light)

Soreness or irritation of the moist linings of the eyes, mouth, vagina, or urethra (urinary tract), sometimes with blistering

Dark patches on the skin that start to blister

If any of these symptoms appear when you are taking penicillin (or a related medicine), stop the medicine and call a health care provider immediately.


Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Allergy skin testing (The Basics)
Patient education: Drug allergy (The Basics)
Patient education: Anaphylaxis (The Basics)
Patient education: Angioedema (The Basics)
Patient education: What you should know about antibiotics (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Allergy to penicillin and related antibiotics (Beyond the Basics)
Patient education: Anaphylaxis symptoms and diagnosis (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Penicillin skin testing
Penicillin allergy: Immediate reactions
Anaphylaxis: Emergency treatment
Fatal anaphylaxis
Overview of cutaneous small vessel vasculitis
Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams

The following organizations also provide reliable health information.

American Academy of Allergy Asthma and Immunology

National Library of Medicine

Mayo Clinic

Literature review current through: Sep 2016. | This topic last updated: Sep 22, 2016.
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