What Is a Drug Allergy?
Drug Allergy and Other Adverse Reactions to Drugs
Many people may use the term “medicine allergy or “drug allergy.” The majority of reactions caused by medications are more correctly termed “adverse reactions to drugs.”
True drug allergies are rare and caused by the immune system.
An allergic reaction is an abnormal response of the immune system to a normally harmless substance. The job of the immune system is to find foreign substances, such as viruses and bacteria, and get rid of them. Normally, this response protects us from dangerous diseases. People with a drug allergy have an over-sensitive immune system. Their immune system reacts to the drug as if it were an invader.
The body’s immune system makes antibodies called Immunoglobulin E (IgE) antibodies. These IgE antibodies react with substances and cause allergy symptoms.
What Causes an Adverse Reaction to Drugs?
There are two broad categories of adverse reactions to drugs:
- True allergic reactions involving the immune system and IgE
(This occurs in a small percentage of people.)
- Non-allergic reactions
(These reactions do not involve allergy or immune reaction to the drug.)
How Does a Doctor Diagnose a Drug Allergy?
If you think you may be allergic to a medicine, tell your doctor. They may recommend that you see an allergist (a doctor who specializes in allergy).
Allergists often make a diagnosis based only upon the patient’s history and the symptoms involved. This is what we call a “clinical diagnosis.”
In many instances, patients may have a reaction while taking several drugs at the same time. In these instances, unless the allergist can identify an allergy to one of the drugs, there is no way to tell which drug is responsible. The doctor then may recommend stopping the suspicious drug or drugs.
Allergy tests can only be useful when the reaction is a true allergic reaction. For specific medications, testing is available to check for IgE. The doctor will consider your medical history, your symptoms and any test results to make a diagnosis.
Tests are only available for a small number of drugs that cause these reactions. One of the most reliable tests we have is the test for penicillin allergy.
Sometimes the allergist will do a drug challenge. A drug challenge is a test where the allergist gives you a small amount of a drug in gradual doses while observing you to watch for a reaction.
If you have a true allergy or a suspected allergy to a drug, stop taking the drug.
What Are the Signs of an Allergic Reaction Due to Drug Allergy?
True allergy to drugs occurs only in a small percentage of people. Other types of immune responses to drugs may also occur.
Classic Allergic Reactions
These reactions occur like other types of allergic conditions such as asthma or hay fever. What is different is that the drug gains access to the whole body rather than just the respiratory tract. Thus, it produces an allergic reaction throughout the body. The classical symptoms of this type of reaction are:
Skin reactions: The most common form of this is hives.
Generalized reaction: This kind of reaction can involve many body systems. This is a serious allergic reaction called anaphylaxis (anna-fih-LACK-sis). Hives are usually present. But, the symptoms also may include:
- wheezing (a whistling, squeaky sound when you breathe)
- shortness of breath
- throat and mouth swelling
- cramping abdominal pain
- fall in blood pressure
Anaphylaxis is the most severe acute form of a drug reaction.
Other Immunologic Type Responses
There are other ways (that are not a classic allergic reaction) the immune system may react to a drug. For example, antibodies to certain drugs can destroy red blood cells. This destruction of red blood cells can cause anemia. The most common type of immune drug reactions are skin rashes (other than hives). These are normally what we call “drug rashes.” In these skin reactions, the skin becomes red, irritated, and bumps may be present. Other types of skin reaction can occur due to drugs. For example, bruises and ulcers can occur as well.
Other Drug Reactions – Adverse Reactions Unrelated to Allergy
There are different types of adverse reactions to drugs that are not a true allergy, including:
- Overdosing: An overdose is taking more than the recommended or prescribed dose. Reactions due to overdosing can be harmful without a person realizing that it’s happening. One of the classical examples of this is overdosing due to acetaminophen (Tylenol®). Overdosing can affect the liver. Often, the patient does not know that they are reacting to an overdose until the condition becomes severe and can cause irreversible damage.
- Expected side effects: Many drugs have known side effects. A classic example is some antihistamines cause drowsiness in a large percentage of patients who take them.
- Indirect effects: A good example of an indirect effect is when antibiotics cause loss of normal bacteria in the bowel. The bacteria loss results in the person developing diarrhea.
- Drug interactions: Drug interactions happen when a person has side effects when taking two drugs together. This commonly occurs when the two drugs metabolize through the same pathway in the liver. For example, the liver metabolizes erythromycin and theophylline through the same pathway. When given together, the metabolism of theophylline slows. The theophylline can reach toxic levels.
- Worsening of a known condition: An example of this is when a person with asthma takes a beta-blocker drug. Beta blockers often worsen asthma.
- Idiosyncratic reactions: Some drugs have a tendency to cause unusual reactions for reasons we do not understand. An example of this is tendon rupture in a patient taking a quinolone antibiotic such as levofloxacin. Quinolone antibiotics have a tendency to cause tendon ruptures. But we don’t know why some individuals are prone to this side effect or how the rupture happens.
Exams and Tests
An examination may show:
Decreased blood pressure
Swelling of the lips, face, or tongue
Skin testing may help diagnose an allergy to penicillin-type medications. There are no good skin or blood tests to help diagnose other drug allergies.
If you have had allergy-like symptoms after taking a medicine or receiving contrast (dye) before getting an x-ray, your health care provider will often tell you that this is proof of a drug allergy. You do not need more testing.
Apart from immediate cessation of the putative drug, the following measures should also be taken:
Acute Immediate Management of IgE-Mediated Reactions
- Nonserious (mild cutaneous) reactions: antihistamines
- Serious reactions (anaphylaxis): emergency management, including securing the airway; maintaining breathing and circulation; and use of drugs, including:
- Intramuscular epinephrine 0.3 mL of a 1:1,000 concentration up to every 5 minutes in adults or 0.01 mg/kg in children up to a maximum dose of 0.3 mg
- Intramuscular promethazine or intravenous diphenhydramine
- Intravenous fluids (colloids or crystalloids)
Systemic corticosteroids may be used to prevent the delayed-phase reaction in acute anaphylaxis and to prevent/treat associated angioedema and lower airway inflammation. This has been extrapolated from its use in acute asthma, with a recent Cochrane systematic review failing to identify any evidence from randomized, controlled trials to confirm the effectiveness of corticosteroids in acute anaphylaxis.
Acute Immediate Management of Non–IgE-Mediated Reactions
- Nonserious reactions: antihistamines
- Serious reactions
- SJS: The use of tapered doses of systemic corticosteroids is not uniformly practiced by all specialists in drug allergy. Oropharyngeal hygiene and gargle solutions, as well as eye care (sterile eye management, use of topical corticosteroids), should be ensured.
- TEN: Skin care, eye care (sterile eye management, topical corticosteroids), adequate hydration and nutrition and respiratory care are paramount. High-dose intravenous immunoglobulin (IVIG 1 g/kg/d for 2 days) has been used at various centers with generally good outcomes, especially in improving skin re-epithelialization. However, the evidence remains controversial, and the original hypothesis on the anti-apoptotic effect of IVIG now does not appear to be so. Other immunosuppressive therapies, including cyclophosphamide, plasmapharesis and systemic corticosteroids, have not been found to be uniformly useful. Recent interest has re-emerged on the possible benefits of ciclosporin provided patients have not developed acute kidney injury and uncontrolled infection.
- DIHS: The use of tapered doses of systemic corticosteroids is not uniformly practiced by all specialists in drug allergy.
Desensitization is a process in which the drug to which the patient is allergic is administered to the patient in small, incremental doses to induce a state of temporary tolerance to the drug. This should only be attempted if the offending drug is deemed essential and no alternatives are available . This treatment has been well established for IgE-mediated drug allergy, specifically to penicillins. Hypotheses as to the mechanisms underlying successful of drug desensitization include mast cell desensitization, hapten inhibition, IgE consumption and mediator depletion.
Drug desensitization for non–IgE-mediated drug allergy has also been described for various drugs. Although treatment has been shown to be effective, the underlying mechanisms for its success remain unknown.
The methods of inducing tolerance are all similar but specifics vary. Assuming that there is a need for the drug that cannot be met in any other way and warrants the risks of desensitization, a schedule is prepared that is appropriate for the clinical circumstances. In some situations, rapid desensitization in a few hours may be required.
Desensitization over a period of days to weeks may be acceptable if the need is for prophylaxis or more chronic treatment. Desensitization via the oral route may be safer than by the parenteral route, but the process is dependent on adequate absorption and may be complicated by vomiting. A beginning dose can be selected as a fraction, possibly 0.1-1%, of the subject ’s known tolerance of the agent or by arbitrarily starting with 1 per 100 to 1 per 1 000 or even less of a therapeutic concentration. Subsequent doses are then increased by approximate doubling. After the therapeutic concentration (dose) is reached, the patient should continue to receive the agent.
Induction of tolerance to the offending drug is temporary – patients should still be regarded “allergic” to that particular drug. Should the patient require the medication 3-7 days after cessation the desensitization process should be reinstituted..
Regimes have been described for many drugs including penicillins, cephalosporins, cotrimoxazole, allopurinol and the chemotherapeutic agents. Following is a list of drugs for which desensitization protocols have been described in the literature: