INTRODUCTION — Serious allergies to penicillin are common. True penicillin allergy is a leading cause of fatal drug reactions. However, many patients who believe they are allergic can take penicillin without a problem, either because they were never truly allergic or because their allergy to penicillin diminished over time.
Patients who have a remote history of allergic reaction to a medication may become less allergic as time passes. Only about 20 percent of patients will be allergic to penicillin 20 years after their initial allergic reaction if they are not exposed to it again during this time period.
TYPES OF PENICILLIN ALLERGY — Several different symptoms may develop after taking penicillin that can indicate that an allergy is present. These include hives (raised, intensely itchy spots that come and go over hours), angioedema (swelling of the tissue under the skin), wheezing and coughing from bronchospasm (narrowing of the airways into the lungs), and anaphylaxis.
Anaphylaxis — Anaphylaxis is a sudden, potentially life-threatening allergic reaction. Symptoms can include very low blood pressure, hives, difficulty breathing, abdominal pain, swelling of the throat or tongue, and diarrhea. Two to 4 percent of allergic reactions to penicillin are of this type. (See "Patient information: Anaphylaxis").
Less severe allergic reactions — A person may develop only hives or only angioedema, without other symptoms, while taking penicillin. This can be a sign that the person is allergic. If they were to take the medicine again, they might develop a more severe reaction, even anaphylaxis.
Rashes — Several different types of rashes can appear while people are taking penicillin. Rashes that involve hives are most suggestive of a true allergy rather than another type of reaction to penicillin. However, some people, especially young children, can develop flat, itchy, speckled rashes that do not involve hives. This type of rash is less likely to indicate a dangerous allergy, although it can be difficult to distinguish between different types of rashes if they happened in the past. Taking a photograph of a rash to show to doctors later is always helpful.
Adverse reactions — Some people have unpleasant side effects (called adverse reactions) after taking penicillin or other antibiotics. Adverse reactions are more common than true allergies, and may include stomach upset or other gastrointestinal reactions. Adverse reactions are not related to allergic reactions, and it is important to distinguish between the two. Persons who incorrectly report that they have had an allergic reaction may then be treated for a particular infection with a less-effective antibiotic. This can lead to antibiotic failure or resistance, which can be costly and prolong illness.
When reporting past problems with antibiotics, it is important to provide as much detail as possible about the reaction. Patients who are uncertain if a past allergic reaction was truly caused by allergy should avoid the antibiotic.
DIAGNOSIS — In some situations, it is necessary to determine with certainty if a person is allergic to penicillin. Testing for allergy is recommended in the following situations: Persons who have a suspected penicillin (or closely related antibiotic) allergy and require penicillin to treat a life-threatening condition for which no alternate antibiotic is appropriate Patients who have frequent infections but have suspected allergies to many antibiotics, leaving few options for treatment
Skin testing — Skin testing is the most reliable method to determine the risk of a serious allergic reaction in a person with a history of allergy to penicillin.
Several different types of penicillin preparations are required for skin testing; most people are allergic to the penicillin break-down products, produced after the drug has been digested. These break-down products can be manufactured commercially but are not currently available in the United States. Thus, skin testing cannot be performed in the United States at this time. It is hoped that the preparations will be available again within the next 12 to 24 months.
Testing procedure — Skin testing should be done by an allergist in an office setting. Testing usually takes three to four hours to complete. The skin is pricked with weak solutions of the various preparations of penicillin and observed for a reaction. If there is no skin reaction, slightly stronger solutions are then used. This is repeated until there is a skin reaction or the testing protocol is completed (with no reactions).
A positive skin reaction is an itchy, red lump that lasts about half an hour and then resolves. The testing is stopped if a skin reaction occurs since this indicates that the person is truly allergic.
If a patient completes the protocol without a positive reaction, a single oral dose of full strength penicillin is usually given. This confirms that the patient does not have an allergic reaction, and is done since there is a very small risk of false negative results (when the skin test is negative although the person is actually allergic).
Safety of skin testing — Skin testing is normally very safe. However, certain people should not have skin testing; a person who is severely allergic to penicillin could develop a dangerous whole-body or anaphylactic reaction. Skin testing is not generally done in people who have a strong history of severe allergy, especially if the reaction happened within the past year. In such patients, an alternate antibiotic should be used, or desensitization to penicillin should be performed if no alternates are acceptable or available. (See "Desensitization" below). Skin testing should not be done in people taking certain medications, such as beta-blockers (eg, atenolol, propranolol, nadolol, esmolol, carvedilol, metoprolol, and sotalol). These medications can interfere with treatment of a severe allergic reaction, were it to unexpectedly occur during testing. Finally, skin testing should not be done in patients with an extensive skin rash since it would be difficult to judge if skin test results were positive or negative.
Penicillin skin testing does not provide any information about certain types of reactions. In particular, a person who has experienced a severe reaction with extensive blistering and peeling of the skin (Stevens-Johnson syndrome or toxic epidermal necrolysis), a widespread sunburn-like reaction that later peeled (erythroderma), or a rash composed of small bulls-eyes or target-like spots (erythema multiforme), should not have skin testing. People with these types of reactions should never again be given the medication that caused the reaction. This applies to all situations since a second exposure could cause death.
Interpreting results — Medical tests, including skin testing, are rarely 100 percent accurate. Most people with a positive penicillin skin test will experience an allergic reaction if given penicillin or a related antibiotic (as would be expected). However, 3 percent of people with a history of penicillin allergy but negative skin tests will also experience an allergic reaction. These reactions are uniformly mild, and anaphylaxis in this situation has never been reported.
OTHER ANTIBIOTICS — Reliable skin tests are not commercially available for antibiotics other than penicillin. Thus, determining if a person has an allergy to other antibiotics is more difficult, and mostly based on the history of the reaction. Skin testing with other antibiotics is sometimes performed, but the results are much less certain than those of penicillin testing. In general, the suspicious drug should be avoided unless life-threatening infections demand their use. In the latter case, desensitization is necessary.
Cephalosporins — Cephalosporins are a class of antibiotics closely related to penicillin. There are a number of cephalosporin medications, a few of which include cephalexin (Keflex®), cefaclor (Ceclor®), cefuroxime (Ceftin®), cefadroxil (Duricef®) , cephadrine (Velocef®). cefprozil (Cefzil®), loracarbef (Lorabid®), ceftibuten (Cedax®), cefdinir (Omnicef®), cefditoren (Spectracef®), cefpodoxime (Vantin®) and cefixime (Suprax®).
People with a positive skin test to penicillin have a high risk of an allergic reaction to cephalosporins, compared to those who have a negative skin test. Those with a history of a cephalosporin allergy who require a cephalosporin should have a penicillin skin test, if available. If the test is negative, the patient should take penicillin (rather than a cephalosporin). If a cephalosporin is required or skin testing is not available, desensitization is recommended.
Monobactams — People who are allergic to penicillin can be given aztreonam (Azactam®), a monobactam, because no significant cross reactivity between penicillin and monobactams has been demonstrated.
Carbapenems — Imipenem and meropenem are carbapenem antibiotics that cross-react with penicillin. Thus, imipenem and meropenem should not be given to people who are allergic to penicillin unless they undergo desensitization. Carbapenems are only given by intravenous injection.
DESENSITIZATION — Desensitization can be done for people who are truly allergic to penicillin but require treatment with it or a closely related antibiotic. Desensitization refers to a process of giving a medication in a controlled and gradual manner, which allows the person to tolerate it temporarily without an allergic reaction.
Technique — Desensitization can be performed with oral or intravenous medications. There are different techniques for desensitization. Some patients undergo desensitization in an outpatient clinic under supervision while others are treated in an intensive care unit.
Limitations — While usually successful, desensitization has two important limitations. Desensitization does not work and must never be attempted for certain types of reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythroderma, and erythema multiforme). (See "Safety of skin testing" above). Desensitization also does not work for other types of immunologic reactions to antibiotics, such as serum sickness, drug fever, or hemolytic anemia. Desensitization is temporary. Allergic reactions to the medication given during desensitization is unlikely as long as it is taken regularly. However, once the antibiotic is stopped for more than 24 hours (times differ slightly for different medications), the person is again at risk for a sudden allergic reaction. Repeat desensitization is required if the same medication is needed again.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Academy of Allergy Asthma and Immunology
(www.aaaai.org) National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html) National Institute of Allergy and Infectious Diseases
(www.niaid.nih.gov) The American Academy of Family Physicians
(familydoctor.org)
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