DRUG ALLERGIES: WHAT ARE THEY?
Allergic reactions to medications are common and have a significant impact on an individual’s health. It is difficult to determine how many people have it in their lifetime, but it is estimated that about 10 out of 100 hospitalised people have a reaction to a drug and 7 out of 100 outpatients.
According to the 1977 classification by Rawlins and Thompson, there are two types of drug reactions. Type A reactions account for about 85-90% of reactions, are predictable and are related to the mechanisms of action of the drug. They can occur in anyone at a given dose (= “adverse reaction”). Next are type B reactions, which occur much less frequently. About 10 to 15% of unpredictable reactions do not depend on the dose and only occur in certain people. Drug allergies fall into this second category. With rare exceptions (for example, certain severe allergies to antiepileptic drugs), they do not have a genetic predisposition or a particular family background. This means, for example, that a family member who is allergic to penicillin will not cause you to develop a penicillin allergy yourself.
Allergic drug reactions can then be divided into two main categories. First, there are the “immediate” allergies, which typically occur within an hour of exposure to the drug in question. The symptoms are characterised by hives (wandering and fleeting skin lesions that itch or even burn), swelling of the face and/or hands/feet, difficulty breathing or even a drop in blood pressure with sometimes unconsciousness (anaphylactic shock) in the most severe cases. These reactions are divided into 4 degrees of severity according to Müller’s classification (I to IV). “Delayed” allergies occur more than one hour and up to several days after the start of the treatment in question. They are characterised by maculopapular exanthema (red skin lesions in patches, firm, often itchy) that can last from several days to several weeks. There are severe forms of delayed reactions with damage to the mucous membrane (mouth, eyes, genitals), severe skin manifestations (blisters, skin scales), fever and sometimes damage to the internal organ ( kidney, liver…).
In these two situations, the reaction mechanism always requires an initial phase of “awareness”. That is, the patient should always have been in contact with the drug for the first time without reacting before developing an allergy on subsequent contact. During immediate reactions, antibodies called “IgE” specific to the drug are formed on first contact and then trigger an immune response the next time the drug is taken. In the case of a delayed allergy, white blood cells, so-called T-cells, are particularly involved in recognising the drug. Since the immune mechanisms responsible for the immediate and delayed reactions are different, the resulting symptoms are also different.
ASSESSMENT AND TREATMENT OF MEDICINE ALLERGIES
The treatment for a severe immediate allergy (breathing difficulties, unconsciousness) is adrenaline by intramuscular injection. Patients with this type of allergy always have a self-injecting adrenaline syringe with them. For less severe forms, antihistamines and cortisone generally help control symptoms. In an emergency, assessment should be supplemented by testing the blood for tryptase, which is released in large quantities during an immediate allergic reaction. It is also important during a severe reaction to note any medications, foods (or insect bites) ingested (or suffered) within two hours of the reaction. Especially in severe reactions, an allergological assessment should be offered after 4 to 6 weeks to clearly identify the allergen responsible for the reaction and define the treatments needed.
Almost one in five people in our population claim to be allergic to penicillin. In reality, however, less than 5% of the population is allergic. This has led to the use of less effective, often more expensive antibiotics, which also have more side effects. In particular, it has been shown that patients who are considered allergic to penicillin are more likely to have post-operative infections. This also has public health consequences with increased healthcare costs, antibiotic resistance and longer hospital stays.
It is also important during a severe reaction to note any medications, foods (or insect bites) ingested (or suffered) within two hours of the reaction. Especially in severe reactions, an allergological assessment should be offered after 4 to 6 weeks to clearly identify the allergen responsible for the reaction and define the treatments needed.Antibiotic allergy Almost one in five people in our population claim to be allergic to penicillin. In reality, however, less than 5% of the population is allergic. This has led to the use of less effective, often more expensive antibiotics, which also have more side effects. In particular, it has been shown that patients who are considered allergic to penicillin are more likely to have post-operative infections. This also has public health consequences with increased healthcare costs, antibiotic resistance and longer hospital stays. It is also important to note that in a given patient, penicillin allergy tends to disappear over the years: By 10 years, 9 out of 10 penicillin allergy sufferers have lost their allergy!
When a patient reports an allergy to penicillin, it is important to know exactly which drug it is, what types of symptoms have occurred – to classify the reaction as immediate or delayed – and finally to determine the severity of the reaction. The continuation of treatment depends heavily on this initial questioning. Depending on the situation, skin tests with different penicillin-based antibiotics may be performed, whether or not followed by a provocation test, to confirm that the drug is well tolerated. This test corresponds to the administration of the medicinal product in small doses under strict medical supervision. In some cases of reactions that do not indicate allergy and / or very old reactions, this test can be performed directly in the waiting room of the doctor specialised in allergology. The search for IgE specific in the blood exists but is of little use for penicillins and for most drugs. For severe delayed reactions, blood tests can be performed (lymphocyte transfor- mation tests) without the patient coming back into contact with the substance in question. At the end of the allergic assessment, the conclusions are recorded in an allergy passport, which is given to the patient.
It should be noted that if there is an immediate allergy to penicillin, there will be cross-reactions with related families. It is estimated that approximately 2% of cross-reactions are with cephalosporins and 1% with carbapenems. These figures, obtained through recent studies, are much lower than those previously published. If you have an immediate allergy to penicillin, these two families of drugs should also be tested. For other antibiotics, note that delayed allergy to Bactrim is relatively common. However, there are no skin tests for this antibiotic. If absolutely necessary, this drug can be re-administered according to a desensitisation protocol. All classes of antibiotics can cause an allergic reaction, with specificities for each class.
One person out of five reports an allergy to penicillin when in reality it is <5%!
Allergy to radiological contrast media
Allergy to contrast media is much rarer than allergy to antibiotics. A good number of reactions that are considered “allergic” are actually type A reactions (e.g., sensation of heat or vagal discomfort). The prevalence for iodinated contrast agents used for scanners, coronary angiography, etc. is 0.15 to 0.7%. and much lower still for gadolinium-based contrast agents used for MRIs, in the range of 0.02 to 0.09% of injections. The vast majority of these reactions are mild, but there are some cases of severe or even fatal reactions. There are immediate and delayed allergies to these products. Allergic assessment can also be done with skin tests, but their sensitivity (ability to detect allergy) is less good than for penicillins. These tests should ideally be done within 6 months of the first reaction. If it is essential to reuse a contrast agent after a reaction, it is generally advisable to use a product other than the one in question during the basic reaction. In case of an immediate reaction, premedication with cortisone and antihistamine is often recommended before the examination.
This treatment does not seem to protect against severe reactions. It has also never been shown to be effective in a delayed reaction and is therefore not recommended in this case. Consequently, in case of a reaction to these products, the opinion of a doctor specialised in allergology is recommended. Finally, let us mention that there is no cross-reaction between iodinated contrast media, seafood, amiodarone and betadine. The iodine in all these products is not the cause of the reaction and there is no a priori allergy to iodine. Similarly, there is no cross-reaction between iodinated contrast media (CT) and gadolinium (MRI), whose chemical structure is completely different.
Allergy and intolerance to anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs are a large family of drugs used in a variety of situations, including pain control. Aspirin is the first in this class of drugs.
In most cases, patients respond to several anti-inflammatory drugs, including aspirin. The reactions consist of an exacerbation of hives, rhinitis or asthma. It is then an intolerance to non-steroidal anti-inflammatory drugs linked to the mechanisms of action of these drugs, namely the blocking of an enzyme called COX-1. Ten per cent of these patients also react to paracetamol (Dafalgan) taken in high doses. It is then up to these patients to find an alternative if needed. Generally, a provocation test with a selective COX-2 inhibitor is suggested.
Less commonly, a patient may have an immediate “classic” allergy to a non-steroidal anti-inflammatory drug mediated by specific IgE. It generally does not respond to other anti-inflammatory drugs. Unfortunately, there is no validated skin test for these molecules and the allergist’s work is often to find an alternative via an oral provocation test.
Intraoperative allergic reaction
If an allergic reaction occurs during surgery, several drugs may be involved. In order of likelihood, it is usually the curares, drugs that take part in the general anaesthetic and are used to release the muscles, that are the cause of the reaction. Next are antibiotics, often given at the beginning of the procedure, followed by latex and chlorhexidine (a disinfectant). If a reaction of this type occurs, it is important to have an allergy assessment a few weeks after the procedure to identify the drug involved and better prepare for possible future procedures. Skin tests are then carried out on most of the drugs used during anaesthesia to find alternatives in case of a new anaesthetic. An allergy passport is then given to the patient.
Drug allergies are relatively common in hospitals and outpatients and their consequences are not negligible. Questioning is essential in management, supplemented by skin tests and possibly a provocation test. However, skin tests are far from available for all drugs. Allergic assessment should ideally be offered in the months following the reaction to give the best chance of specifying the drug in question and finding alternatives in case of future needs.
Dr. Annette Leimgruber-Bosset
Immunology & Allergology, CHUV, Lausanne