Drug allergies: how to recognize them and how to get around them

Infrequent, but risky, drug allergies are unpredictable individual reactions that should not be underestimated.

Fortunately they are rare. But unfortunately, in the few cases in which they occur, allergies and hypersensitivity reactions to drugs can represent a problem of some importance: not only for the possible immediate more or less severe inconveniences resulting from the abnormal immune reaction, but also because they preclude the possibility of taking again the active ingredient that caused the allergy and all compounds with a similar molecular structure or mechanism of action.

This means that a person allergic to a drug sees the range of therapeutic options that can be used to treat common disorders or specific diseases decrease, being able to find it extremely difficult to identify valid and safe alternatives if the active ingredients that have determined the sensitization are more than one or if there are no well-tolerated molecules with different characteristics able to determine the necessary therapeutic effect.

Why can a drug give allergy?

Like any other substance present in the environment, even the active ingredients of drugs or, more rarely, their excipients can behave as sensitizing agents or real allergens after being inhaled, ingested, instilled, injected into a vein, intramuscularly or subcutaneously or applied to the skin or mucous membranes.

This possibility is always present, albeit with a different degree of probability for the different preparations, despite the fact that all medicines are developed with a view to making them as tolerable as possible and are tested on thousands of people before marketing authorization to verify their safety on all fronts, including the immunological one (one of the main ones to which attention is paid).

This happens because the allergic reaction that can occur in a minority of people does not depend on the drug itself, but on the individual immune response, essentially unpredictable before the drug is taken for the first time.

An allergic reaction to a drug, however, can also occur after years of serene use of the same medicine or similar medicines, also in this case following an abnormal and unpredictable activation of the immune system.

In addition to having their own allergies, drugs can give rise to hypersensitivity reactions, linked not to their molecular characteristics and to the production of immunoglobulins typical of allergy (IgE) or to the activation of other immune mechanisms (non-IgE-mediated allergy), but to the mechanism of action of the drug itself. This phenomenon is quite common among users of non-steroidal anti-inflammatory drugs (NSAIDs), especially in the case of high-dose or prolonged therapies.

Specifically, hypersensitivity, which manifests itself mainly with itchy skin rash or more or less extensive urticaria and variable localization, is secondary to the inhibition of cyclooxygenases 1 and 2 (COX 1 and 2), the enzymes that transform arachidonic acid into prostaglandins and thromboxanes, the main substances that trigger and support inflammation.

While extinguishing inflammation and pain thanks to the blockade of COX 1 and 2, NSAIDs indirectly increase the amount of arachidonic acid and the production of leukotrienes, compounds involved in both inflammation and histamine-mediated allergic response. In sensitive individuals, this can mimic an allergic response.

In addition to antibiotics and NSAIDs, among the drugs that can most often give allergic or hypersensitivity reactions are:

  • Antipsychotic
  • Antidepressants
  • Opioids
  • insulins
  • antitumors and immunomodulators (in particular, monoclonal antibodies)
  • antihypertensives (ACE inhibitors)
  • heparins and other anticoagulants
  • contrast media used in radiology.

When to suspect a drug allergy

In most cases, commonly used medicines are well tolerated and do not create problems of some kind, if used correctly and only when they are really needed. However, as the package inserts clearly show, any prescription or over-the-counter drug can sometimes cause side effects related to its metabolism or to unwanted secondary actions exerted in addition to the therapeutic effect.

Distinguishing a non-immunological side effect from an allergy to a drug may not be simple, but there are some criteria that can guide the interpretation. First of all, it is very likely that you are facing an IgE-mediated allergy if within 30-60 minutes of taking the drug by mouth appear:

  • Reddened and itchy skin spots
  • urticarial wheals
  • itching and swelling of the lips and face
  • respiratory manifestations of asthmatic type.

In very few cases of extreme sensitivity to the medicine, it can lead to anaphylaxis.

Sometimes, the same reactions can occur after a certain number of intakes, or even occur a few days after stopping a course of therapy. In this case, it may be a delayed, non-IgE-mediated allergy supported by certain subtypes of immune system cells (T lymphocytes).

In all these cases, it is essential to go immediately to the emergency room, bringing with you the drug taken and indicate exactly to the health personnel the dosage used, the time and the modalities / timing of the onset of symptoms.

The report to the doctor can be considered less urgent only if the reaction is limited to the skin and is very mild (few reddened spots or small bumps and minimal itching), but it should still be provided as soon as possible, also to know how to behave in the subsequent management of the disease that was being treated.

But was it really allergy?

Unfortunately, there are no laboratory tests that can establish with absolute certainty if a person is allergic to a drug, especially when the result obtained is negative, since it could be a false negativity. In addition, currently available tests can only provide information for a limited number of drugs.

In fact, a person is considered “potentially allergic” or hypersensitive to a certain drug or class of drugs only after the typical allergic manifestations have occurred, taking into account the characteristics, age and sex of the patient, the possible presence of other allergies or specific diseases and the circumstances in which the drug was taken.

For some active ingredients, tests carried out on the blood are available that allow in part to guide the interpretation of the observed manifestations: these are the RASTs (similar to those performed for environmental and food allergens) and cytotoxicity tests called “basotest”. The latter, however, are still used in an experimental context and the information they provide is reliable only if the outcome is positive (confirmed allergy), while if they are negative they have no value.

Other useful allergy tests are skin tests such as Prick and Patch, which involve subcutaneous administration with small needles of diluted quantities of the suspect active ingredients: the Licks give the result in 10-15 minutes while the Patches require checks of the skin reaction by the allergist after 48 and 72 hours.

In all cases where there is even a marginal suspicion of allergy to a drug, it is necessary to avoid taking that drug and those with similar structure / mechanism of action, even if the first allergic manifestations were mild, because further use can give rise to more severe effects, up to anaphylaxis.

To identify alternative drugs to use, one must undergo “intake tests” in a protected hospital environment, generally performed in day hospital.

Joycelyn Elders is the author and creator of EmpowerEssence, a health and wellness blog. Elders is a respected public health advocate and pediatrician dedicated to promoting general health and well-being.

The blog covers a wide range of topics related to health and wellness, with articles organized into several categories.

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