Medication allergy

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
  • Overdose
  • Side effects
  • Indirect effects, related to the medication or to the disease
  • Medication interactions
• Unpredictable reactions:
  • Intolerance
  • Idiosyncratic
  • Allergic hypersensitivity
  • Non-allergic hypersensitivity (pseudoallergy)

In this summary we predominantly cover 2 types of hypersensitivity which are particularly specific to our specialty.

Allergic hypersensitivity

These reactions can be classified according to their incidence and their varied clinical expression:

• An itchy, maculopapular rash (delayed type IV reacions), responsible for about 70% of medication allergies
• An immediate reaction often appearing within an hour after taking the medication (type I reaction):
  • 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 (type IV):
    • SCAR: severe cutaneous adverse reaction. In certain cases there is an association with genetic markers called HLA, so these reactions are predictable if we look for the markers before using the medication.
  • Severe to moderately severe reactions:
    • Vasculitis and serum sickness (often type III reactions)
    • Immune cytopenias (often type II reactions)
    • Hepatitis, nephritis, pneumonitis, medication related meningitis (often type IV reactions).
  • Less severe reactions:
    • Fixed drug eruption
    • Baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE)

Non-allergic immediate 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 (mediated by blocking the enzyme cyclooxygenase) 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. This test is more often positive with recent reactions.
  • In the case of an immediate pseudoallergic reaction, skin testing does not exist.
  • 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. The more severe the reaction, the greater the chance the test is positive.
• 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.

In many cases a diagnosis of allergy has previously been given on a clinical basis only, and this diagnosis can be challenged with proper investigation. A very common example is a history of a rash while taking penicillin in children, and sometimes adults. In many cases the rash is viral and a medication challenge is negative. Additionally, in many cases, the medication allergy may disappear.

Treatment and management in the case of a medication allergy or pseudoallergy

• In the acute phase of the reaction :
  • Stopping the medication in question in the first thing to do in general.
  • Certain medications can be given to improve symptoms or reduce the allergic reaction, such as antihistamines, and sometimes cortisone.
  • In certain cases, when the medication is essential and the reaction is mild, one may opt to continue with close follow-up and symptomatic treatment: at any moment if the reaction worsens, one should stop the medication.
• It is generally recommended to specifically identify as being allergic to the medication in question, and to avoid it. You can wear a bracelet identifying the allergy, or carry a document that identifies the medication to which you are allergic, as well as the type of allergic reaction, and the date of the reaction. These facts should also be available in your medical chart.
• In certain cases where a medication is important and the allergy or pseudoallergy is confirmed or strongly suspected, one can reintroduce the medication in question using a desensitization protocol. The following are some examples of these situations:
  • An immediate reaction to penicillin or another antibiotic
  • An immediate reaction to platinum salts (chemotherapy)
  • An immediate pseudoallergic reaction to taxanes (chemotherapy)
  • An immediate pseudoallertic reaction to anti-inflammatory medication
  • Certain delayed reactions that are not very severe; severe delayed reactions such as SCARs are a contraindication to desensitization.

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André Caron, MD FRCPC
(translation: Andrew Moore, MD FRCPC)

Updated 12/2024