Drug Allergy

When the immune system reacts, a drug is viewed as a chemical "invader," or antigen. This overreaction is often called a hypersensitivity reaction.

• An adverse reaction to a drug is any unintended effect of a drug, not including failure of the drug to work, abuse of the drug, or overdose of the drug. Adverse reactions to drugs include both drug allergy and drug intolerance.

What are the signs of allergic reactions to medication?

• A drug allergy is caused by the immune system reacting to a drug. There are several different types of drug allergies that lead to allergic reactions. Reactions to drugs range from mild, localized rash to serious effects on different organ systems. The skin is the most frequently involved organ.
• A drug intolerance is an unwanted side effect of a drug that is not caused by the immune system or problems with the metabolism of the drug. An example of drug intolerance is nausea with opioid medications (narcotic painkillers), such as morphine.
• Other types of adverse reactions to drugs include interactions between two or more drugs and the inability to break the drug down completely in the body (as occurs with liver or kidney damage).

How do you get tested for a drug allergy?

• If you have experienced any adverse reaction to a drug, it is helpful to describe it in detail to help medical professionals accurately classify the symptoms.

It is important to recognize the symptoms and signs of a drug allergy, because they can be life-threatening, but few adverse reactions to drugs are actually allergic in nature. A true allergic reaction to a drug does not happen the first time you take a medication, but reactions similar to an allergic reaction may occur. A reaction is much more likely to occur after your body has been exposed to the medication at least once.

When the immune system reacts, a drug is viewed as a chemical "invader," or antigen. This overreaction is often called a hypersensitivity reaction.

IgE-Mediated Reaction

In one type of hypersensitivity reaction, called an IgE-mediated reaction, the body produces an antibody (called IgE) to the drug. The IgE antibody is produced on the first or subsequent exposures to the drug. When the body is exposed to the drug again, the previously formed antibodies recognize the drug and signal the cells to release chemicals called mediators. Histamine is an example of a mediator. The effects of these mediators on cells and organs cause the symptoms of the reaction.

The most common medications leading to allergic reactions from IgE-mediated reactions include the following:

• Antibiotics such as penicillin and sulfa drugs
• Biologic medications for autoimmune diseases such as infliximab (Remicade)
• Chemotherapy medications (cisplatin [Platinol-AQ, Platinol] or oxaliplatin [Eloxatin])
• NSAIDs (nonsteroidal anti-inflammatory medications), such as ibuprofen or naproxen

Delayed Hypersensitivity Reaction

Another type of hypersensitivity reaction, called a delayed hypersensitivity reaction, occurs when a different part of the immune system, the T cell, recognizes the drug antigen. This type of hypersensitivity response leads to the release of chemical mediators called interleukins and cytokines. This type of reaction happens over days to weeks, unlike the IgE-mediated reactions described above, which occur more quickly. This type of reaction most commonly affects the skin but can also affect the kidneys, lungs, liver, and heart. Certain types of this reaction can also lead to severe skin involvement with blistering and peeling of the skin. These severe reactions are a spectrum and are also referred to as Stevens-Johnson syndrome and toxic epidermal necrolysis.

The most common medications leading to allergic reactions from T cells are

• antibiotics such as penicillin and sulfa drugs,
• antiseizure medications such as lamotrigine (Lamictal), and
• topical antibiotics or topical steroids (these usually cause isolated skin reactions).

Immune Complex Reaction

A rarer type of hypersensitivity reaction occurs when antibodies in the blood recognize the drug and bind to it, creating "clumps" of antibody and antigen. This type of reaction, called an immune complex reaction or a serum sickness-like reaction, leads to symptoms such as joint pain, fever, and hive-like lesions on the skin. This type of reaction can also be caused by antibiotics and biologic agents used to treat autoimmune diseases.

Other Types of Reactions

Other less common types of reactions to medications can lead to destruction of red blood cells or platelets due to interactions between antibodies and a drug. This is known as autoimmune hemolytic anemia. Another type of drug reaction causes inflammation in the lungs due to an immune response to a drug, known as pulmonary drug hypersensitivity. The eosinophil, which is a type of white blood cell, can also be involved in a severe hypersensitivity response to a drug, affecting the skin and other organs, and this is medically termed drug rash with eosinophilia and systemic symptoms (DRESS).

Risk factors for drug allergies include

• frequent, but intermittent exposures to the drug;
• large doses of the drug;
• drug given by injection or intravenously rather than by a pill, tablet, or capsule;
• genetic factors; and
• a history of allergies or asthma in some cases.

Drug allergies may cause many different types of symptoms depending on the drug and its administration, patient characteristics, and the part of the immune system causing the reaction.

IgE-Mediated Symptoms and Signs

Skin symptoms with this type of reaction include hives, itching, flushing, lip swelling, tongue swelling, or eye swelling.

A severe IgE-mediated reaction is called anaphylaxis or an anaphylactic reaction. This is a serious allergic reaction that can be life-threatening. A person with anaphylaxis must be treated in a hospital emergency department. Characteristics of anaphylaxis (sometimes referred to as anaphylactic shock) include the following:

• Skin symptoms: hives, redness/flushing, swelling, sense of warmth, itching
• Respiratory symptoms: chest tightness, cough, wheezing
• Gastrointestinal symptoms: vomiting, diarrhea, abdominal pain/cramping
• Cardiovascular symptoms: lightheadedness or loss of consciousness due to low blood pressure ("shock"), rapid or irregular heartbeat

Most anaphylactic reactions occur within minutes to hours of taking the drug.

Delayed Hypersensitivity Symptoms

Skin symptoms of delayed hypersensitivity reactions include an itchy rash that can be flat, bumpy, or both; blistering oral sores, lesions on the skin that look like bull's-eye targets, and bruise-like lesions on the skin.

Other symptoms: Depending on the drug and severity of the reaction, there may also be kidney involvement, lung involvement, cardiac involvement, eye involvement, or gastrointestinal involvement.

Immune Complex Symptoms

Skin reactions of immune complex reactions include painful hive-like lesions and lesions that look like bruises.

Other symptoms can include joint pain, joint swelling, fever, and swollen lymph nodes.

• Usually the prescribing medical professional will recommend that you stop the medication, and he or she may prescribe an alternate medication if needed.
• If you cannot reach this provider for advice quickly and you are concerned about your symptoms, go to an urgent care or an emergency department. If you are having any symptoms of an anaphylactic reaction discussed above, call 911.

Generally a drug allergy is diagnosed by signs and symptoms. Medical professionals are trained to recognize symptoms that fit a particular type of drug reaction pattern.

Blood tests and imaging (X-rays, ultrasound, CT scans) are needed sometimes to evaluate which body systems may be involved in a reaction.

There is accurate skin testing that can be performed by an allergist to determine if an IgE-mediated reaction to penicillin occurred. Some allergists may order skin tests to other medications, as well.

The main treatment for drug allergy is stopping the suspected drug. Mild reactions may be treated at home. For itching, an antihistamine such as diphenhydramine (Benadryl), cetirizine (Zyrtec), or fexofenadine (Allegra) may be recommended. For more involved skin symptoms, sometimes oral steroids (prednisone) may be indicated.

Moderate to severe reactions require immediate medical attention.

• Some severe hypersensitivity reactions may require hospitalization.
• Anaphylaxis to a drug needs to be treated quickly with epinephrine.
• Patients with anaphylaxis need monitoring for an appropriate time period after the reaction. They are usually treated with steroids and antihistamines, as well.
• Other severe skin reactions or drug reactions with other organ involvement may require hospitalization and directed treatment. Also, steroids may be necessary for treatment.

Follow up with your healthcare provider after an allergic reaction to a drug. At this follow-up appointment, he or she can evaluate your recovery from the reaction and adjust any medications.

If you do not respond to the treatment prescribed for your drug allergy, it is important that you see a medical professional for reevaluation.

There is no known way to prevent drug allergies. Always tell any new healthcare provider you see about your allergies and the types of reactions you have had. Keep a list of symptoms encountered with previous drugs. Do not take a drug that you have reacted to in the past unless advised by an informed medical professional. In the case of a severe reaction history, consider wearing a medical alert ID bracelet or necklace. These devices are worn on the wrist or neck and can alert medical personnel and others about the risk of an allergic reaction.

Tell your healthcare provider about any medications (prescription or over-the-counter) that you are taking.

Most people who have mild to moderately severe allergic reactions to a drug do very well with prompt recognition and treatment.

Penicillin Allergy

There is currently significant interest in penicillin allergy due to the cost of alternative antibiotics and the presence of resistant bacteria. Approximately 10% of the U.S. population reports a penicillin allergy. When thoroughly evaluated, however, more than 90% of patients with a penicillin allergy can tolerate penicillin-based antibiotics without difficulty. There are two common reasons for this misdiagnosis: individuals lose their penicillin allergy over time, or the initial reaction was not truly caused by penicillin. A penicillin allergy "label" not only limits an individual's choice of antibiotics but also puts individuals at risk of longer and costlier hospitalizations and puts them at greater risk for severe diarrhea caused by a bacteria called Clostridium difficile, also known as C. diff. Unlike many medications, there is excellent testing for penicillin allergy that can be performed by an allergist. Individuals with penicillin allergy should discuss the utility of this testing with their healthcare providers.