Medications are means of treatment or indispensable investigation in contemporary medicine. However, despite their incontestable benefits, they are still responsible for a number of adverse reactions.
Classification of adverse reactions
These can be classified in the following manner:
- Predictable reactions
- Side effects
- Indirect effects, related to the medication or to the disease
- Medication interactions
- Unpredictable reactions:
- Allergic hypersensitivity
- Non-allergic hypersensitivity (pseudoallergy)
These reactions can be classified according to their incidence:
- An itchy, maculopapular rash, responsible for about 70% of medication allergies
- Urticaria and angioedema, responsible for about 25%, which can lead to anaphylaxis, representing less than 5%
- Other kinds of reactions, representing about 5%. Some examples include:
- Very severe reactions:
- SCAR: severe cutaneous adverse reaction
- Moderately severe reactions:
- Immune cytopenias
- Less severe reactions:
- Fixed drug eruption
- Baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE)
Non-allergic hypersensitivity (pseudoallergy)
Certain medications can cause a reaction similar to an IgE-mediated reaction, without actually implicating an IgE-mediated mechanism. These are called "pseudo-allergic". This kind of reaction is seen frequently in the clinic, and can exist as 3 principal groups:
- Reactions mediated by histamine (urticaria and angioedema, possibly leading to anaphylaxis), such as reactions to narcotics, to certain antibiotics (vancomycin), and several reactions to radiological contrast agents.
- Reactions to anti-inflammatories and to aspirin can cause respiratory symptoms, worsening asthma or rhinitis, or skin reactions such as urticaria or angioedema.
- Reactions mediated by kinin, such as a disabling cough, or angioedema of the face, tongue or throat; these reactions principally occur with medications inhibiting metabolic pathways of kinin, such as ACE inhibitors (inhibiting the angiotensin converting enzyme), leading to a cough or angioedema, or ARB medications (angiotensin receptor blockers) that can cause angioedema.
Investigation of medication allergy
- The first step is to obtain as much information regarding the reaction as possible; clinical and laboratory manifestations, timing, if any other medications were taken during the reaction, its evolution and treatment. Sometimes the clinical history is sufficient, especially if the reaction occurred more than once with the same medication.
- From there, allergy tests may be useful according to the kind of reaction, its cause, and the suspected medication:
- In the case of an immediate reaction thought to be IgE-mediated, a skin test, followed by intradermal testing, might be undertaken. The sensitivity of this test varies from one medication to another, and a negative test doesn't always signify the absence of allergy.
- In the case of a delayed reaction, such as a maculopapular drug eruption up to SCAR, skin application tests (patch tests) and intradermal testing with delayed reading of 24 hrs or more can be considered. Here, a negative test does not exclude an allergy, but a positive test can be very significant.
- Finally a challenge test may be considered, if not thought to be too dangerous: this consists of exposing the patient to the medication in question. Different protocols exist according to whether the reaction was immediate (urticaria or anaphylaxis), or a delayed reaction such a maculopapular rash, or other.
It is important to properly identify a medication to which one has had an allergic reaction, in order to avoid it in the future. In many cases, an allergist can help to make the diagnosis of a medication allergy, and can also give important information in the case where treatment might be necessary with a medication that may have caused a prior allergic reaction.
André Caron, MD FRCPC
(translation: Andrew Moore, MD FRCPC)