What Is Drug Allergy?

Introduction

Any reaction produced by a medication exhibiting clinical traits associated with hypersensitivity is called a drug allergy. It is quite important to gather information about drug sensitivity allergies to prevent accidentally prescribing, distributing, and administering an inappropriate drug to individuals at risk. Drug allergy research strongly relies on a thorough clinical history that must contain information on the rash and onset of symptoms, along with the number of doses of the drug that were taken prior to the reaction.

It is essential to differentiate between drug allergy and drug intolerance or sensitivity. While drug allergies are defined as adverse drug reactions with a known immunological mechanism by the British Society for Allergy and Clinical Immunology (BSACI), drug intolerance or sensitivity refers to an inability to tolerate the side effects of a medication, typically at therapeutic or sub-therapeutic doses.¹

Additionally, one should distinguish between side effects caused by a medication and drug allergies. A drug allergy always has a negative effect and always involves the immune system. It only affects certain people. On the other hand, everybody taking a certain medication runs the risk of experiencing a side effect which usually excludes the immunological system. Any medication action, whether beneficial or negative, that is unrelated to the drug's primary function is referred to as an adverse drug reaction.²

Types of drug allergies

According to their onset time, drug allergies can be classified into immediate and non-immediate or delayed reactions. While non-immediate drug hypersensitivity reactions (DHRs) can occur from more than 1 hour to many weeks after evoking treatment, immediate DHRs typically occur between 1-6 hours following drug administration.³

Immediate hypersensitivity reactions

Nearly all kinds of therapeutic medicines, including antibiotics, anticonvulsants, anaesthetics, neuromuscular blocking drugs (NMBD), chemotherapeutic agents, and non-steroidal anti-inflammatory drugs (NSAIDs), have been associated with immediate onset hypersensitivity.⁴

The majority of immediate allergic drug hypersensitivity reactions (ADHRs), which are also known as type I reactions, take place within the first hour of the administration of a new medication.

• Anaphylaxis

Anaphylaxis is a severe form of immediate hypersensitivity. Massive histamine release is involved in this potentially fatal reaction, which can cause breathing problems and low blood pressure. Anaphylaxis usually includes multiple target organs, such as the skin, respiratory, gastrointestinal, cardiovascular, and nervous systems. It is manifested through swelling, hives, lowered blood pressure, and in severe cases, shock.

• Urticaria (hives)

The second most frequent cutaneous manifestation of drug allergy is urticaria (hives). It usually results from penicillins, sulfonamides, and nonsteroidal anti-inflammatory medicines within 24 hours of drug consumption.⁵ Hives are welt-like, with elevated red spots or bumps on the skin. They are a sort of swelling that appears on the skin's surface and are brought on by an allergic reaction. Chronic hives are welts that last longer than six weeks and frequently come back over the course of months or years.

Delayed hypersensitivity reactions

Delayed drug hypersensitivities are mostly the result of T-cell mediated reactions which vary in severity and clinical diagnoses such as maculopapular exanthema (MPE), fixed drug eruption (FDE), single organ disease (e.g., drug-induced liver injury (DILI) and kidney diseases), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

• Maculopapular rash

A macule is a flat, reddish spot of skin that appears as part of a rash. In a rash, a papule is a raised patch of skin. A rash with both flat and elevated areas is referred to as maculopapular. Depending on the root cause, a maculopapular rash can arise anywhere on the body and can spread to other locations. The rash normally lasts between 2 and 21 days.

• Fixed drug eruption

A single (or limited number of) well-defined, round or oval, reddish or violaceous patch or plaque that may blister or ulcerate is a sign of a fixed drug eruption. Oral pharmaceuticals are the most prevalent cause of fixed drug eruption, with antimicrobials and nonsteroidal anti-inflammatory drugs (NSAIDs) being the most prominent causes. Topical or intravaginal medication exposures are less common causes. 

• Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

The most severe delayed medication responses not only produce rashes, but they can also affect other organs such as the liver, kidneys, lungs, and heart. Blisters are a symptom of dangerous drug reactions called Stevens-Johnson Syndrome and toxic epidermal necrolysis (TEN), in which the surfaces of the eyes, lips, mouth, and genital region may get damaged.

Common allergenic drugs

Antibiotics

Penicillin is a widely used antibiotic that treats bacterial illnesses such as pneumonia, scarlet fever, respiratory tract infections, and others. Penicillin and similar antibiotics are among the most commonly used medications that induce drug allergies.

Sulfonamides can cause delayed hypersensitivity reactions such as Stevens-Johnson syndrome. People who develop an allergic reaction to a sulfonamide antibiotic are sometimes labelled as "sulfur allergic" or allergic to sulfur, sulphur, or sulfa. This phrase should not be used since it is unclear and may lead to confusion. Some people mistakenly believe they will be allergic to non-antibiotic sulfonamides, as well as other sulfur-containing medications or sulfite preservatives.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or naproxen, have the potential to cause allergic responses. It's worth noting that persons who are allergic to aspirin are also likely to be allergic to other NSAIDs.

Other common allergenic drugs

Other medications that most often cause a reaction include:

• Local anesthetics
• General anaesthetics
• Insulin
• Chemotherapy drugs
• Acetylsalicylic acid

Risk factors for drug allergies

Age, gender, genetic polymorphisms, certain viral infections ((HIV and herpes viruses), and drug-related characteristics (e.g., frequency of exposure, mode of administration, molecular weight) are all factors that have been linked to an increased chance of developing a drug allergy. Drug allergies are typically observed in young and middle-aged individuals and are more common in women than males.⁶ A history of other allergies, such as food allergies or hay fever, as well as a personal or family history of medication allergy, can also raise the risk. Oral administration of drugs is less immunogenic than topical and intravenous/intramuscular treatment. 

Symptoms and clinical presentation

In many situations, it might be challenging to identify whether a reaction is brought on by the drug or something else.

The most common symptoms of a drug allergy include:

• Hives
• Rash
• Irritation
• Itching of the skin
• Itching of the eyes
• Swelling in the mouth and throat
• Sneezing
• Redness
• Bleeding
• Congestion
• Difficulty in breathing
• Feeling faint, light-headed or “blacking out”
• Anxiety

Diagnosis

For an appropriate diagnosis of a drug allergy, you should consult with your healthcare professional and let them know about the following:

• When the symptoms started
• What they felt like
• How long they lasted
• Any other prescriptions you took during that time, including any over-the-counter medications
• If you have a family history of drug allergies
• If you have had an allergic reaction to other drugs or allergens in the past

Skin testing

During allergy skin tests, the skin is exposed to suspected allergy-causing substances (allergens) and then examined for symptoms of an allergic reaction. A skin prick test, often known as a puncture or scratch test, looks for rapid allergic reactions to up to 50 different chemicals at the same time.

Blood tests (serology)

Blood testing (in vitro immunoglobulin E antibody tests) can be appropriate for patients who should not or cannot undergo skin tests. These tests are not utilized to diagnose penicillin allergies.

Management and treatment

Topical corticosteroids and oral antihistamines may improve cutaneous symptoms of allergic drug reactions.⁶

If you have severe hives or hives that last for more than a few days, seek advice from a medical professional.

Treatment of anaphylaxis must begin immediately. If you experience an anaphylactic reaction, you should get an epinephrine (adrenaline) shot right away, and someone else should dial 911 for immediate medical assistance. If neglected, it can be fatal.

As per the NICE Drug Allergy: diagnosis and management clinical guideline⁷, people should be referred to a specialized drug allergy service if they have:

• a possible anaphylactic reaction or
• a severe non-immediate cutaneous reaction, such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms (DRESS).

Prevention

Precautions to take to reduce the risk of developing drug allergies include:

• Avoiding known triggers. If it is known which medication has caused the drug allergy, the person should try to avoid that substance.
• Healthcare professionals should include information about the potential drug allergy in the patient's medical records.
• Healthcare professionals should give patients written details about their allergies, including information on drugs they should avoid.
• Before receiving any form of medical treatment (including dental care), it's critical that the patient discloses to their doctor any medication sensitivities they may have. It's also a good idea to carry a card with information about the allergy or wear a medical alert bracelet or pendant.

Summary

Any drug, both over-the-counter and prescription medication, can cause drug allergies in some people. Even if a person has used a drug in the past without incident, they can still experience an allergic reaction to it. Some allergic responses might occur shortly after taking the medication and can take a variety of forms, such as a red, itchy rash or swelling of the lips and eyelids. Very rarely can someone experience a severe reaction known as anaphylaxis. Other allergic reactions may not manifest for days or even weeks. However, if a person has already experienced an allergic drug reaction in the past, they can appear sooner. The most effective strategy to treat a drug allergy is to identify and avoid the allergenic drug substance. When available, alternative drugs with unrelated chemical structures should be used.

If you have signs or symptoms of a drug allergy, see your doctor as soon as possible. It is critical to understand and discuss what constitutes an allergic reaction, a common side effect, and what you can tolerate when taking specific medications.

FAQs

1. What is the most common drug allergy?

The most frequently reported medication allergy is penicillin.⁸

2. How long does it take for a drug allergy to manifest?

It varies. Some people develop an allergy to a drug the first time they take it. Others might not experience a reaction until their second or even multiple exposures.

3. Can drug allergies be spread to another person?

No, drug allergies aren’t contagious. A drug allergy cannot be transferred to another individual.