Drug allergy Dr Adrian Morris Around 15 per cent of patients hospitalised in the UK report adverse reactions to medication, but less than five per cent of those reports are true allergic reactions (mostly to antibiotics). Of this five per cent, less than one per cent are fatal.

In this article

Types of reaction What are the symptoms?

What's the treatment? Can they be prevented?

Latex allergy Salicylate intolerance

Adverse reactions to drugs can be divided into three groups:

• Those not related to the drug at all, but coincidental and due to other factors, for example, rashes or nausea associated with the disease and not the medication
• Common predictable reactions, such as from taking an overdose, or owing to side-effects or interactions with other medications (known as type A drug reactions)
• Uncommon and unpredictable reactions, of which many are allergic reactions involving the immune system and may be either immediate or delayed (type B drug reactions)

Allergic reactions vary from slight rashes to severe anaphylactic immune reactions, such as those seen with penicillin, blood transfusions and intravenous fluids.

Other medicines can trigger histamine release in the body by non-immune mechanisms. No diagnostic blood tests are available for these.

Medications implicated here include aspirin and anti-inflammatory drugs, morphine and the opiate family, anaesthetics and some fluids given intravenously during x-ray.

Drugs that cause allergic reactions include:

• Antibiotics - penicillin, sulphonamides, tetracycline, chloramphenicol and cephalosporins
• Heart drugs - ACE inhibitors, quinidine, amiodarone, methyldopa
• Anaesthetic drugs - muscle relaxants, thiopentone, halothane
• Morphine derivatives - morphine, pethidine and codeine
• Aspirin-like drugs - diclofenac, ibuprofen, indomethacin
• Cancer chemotherapy drugs - cisplatin, cyclophosphamide, methotrexate
• Antiseptics - chlorhexidine, iodine
• Vaccines - such as tetanus toxoid and diphtheria vaccine
• Preservatives and colourings in medication - such as sulphites, sodium benzoate and tartrazine
• Anti-epileptic, anti-tuberculosis medication, heparin, insulin, enzymes and latex

Although commonly reported, allergic reactions to dental local anaesthetics are uncommon and adverse reactions are usually from the additives (sulphites or parabens) or a side-effect of the adrenaline (especially if the anaesthetic is inadvertently injected into a vein instead of the skin).

Most reactions occur within one hour and involve a measles-like itchy rash or urticaria with swelling (angioedema).

A severe life-threatening reaction may involve fever and generalised skin blistering with peeling (toxic epidermal necrolysis and Stevens-Johnson syndrome). A reaction may progress to life-threatening anaphylaxis and even death.

Delayed reactions can develop up to two weeks after exposure to the drug, with generalised dermatitis and damage to vital organs such as the kidneys, liver and blood cells.

Some medications can cause a fixed drug eruption, with a patch of rash occurring at the same spot every time you take that particular drug.

Treatment involves immediate withdrawal of the implicated drug, followed by antihistamine medication. In cases of anaphylaxis, the prompt use of adrenaline and steroids is life-saving.

Most medications are chemicals that bind with various proteins in our body, called haptens. It's this drug/hapten complex that may trigger an allergic reaction.

As a consequence, these reactions are difficult to recreate on the skin or in a blood test, so blood testing for drug allergies is unreliable and inaccurate, with false positive and negative results.

Sometimes the drug will only cause a reaction under specific circumstances. For example, amoxicillin when given in glandular fever may trigger a generalised rash, while tetracycline in association with direct sun exposure may trigger a rash.

Only penicillin, amoxicillin, sulphonamide and cephalosporin allergy can be checked by skin and RAST testing, and in such cases still has only 50 per cent reliability.

To confirm an allergy to a drug, intradermal skin testing, followed by drug provocation tests (DPT) in hospital, is needed. This is time-consuming and expensive, and may trigger a severe allergic reaction. A blood test called tryptase can confirm an allergic reaction has taken place if done immediately.

Patch tests on the skin can test sensitivity to certain skin medications such as local anaesthetics, neomycin, lanolin and paraben preservatives.

If you're allergic to a member of a family of drugs such as penicillin or aspirin, all other members of that family should be avoided unless negative provocation challenge tests have been performed.

If you're allergic to penicillin, use the erythromycin family of antibiotics instead. The same goes for allergy to anti-inflammatory medication such as ibuprofen - only use paracetamol.

It's possible to have an allergic reaction to almost any drug, including paracetamol, so only use medication if absolutely necessary or if it has been specifically prescribed to you. Never use someone else's medication unless you have taken medical advice and are sure it's safe to use.

Occasionally, when it's vital that a penicillin-allergic person receives penicillin, 'rush' penicillin immunotherapy or desensitisation may be undertaken in a hospital ITU unit.

This involves injecting the person with penicillin, starting with minute traces and doubling the dose every few minutes until a state of tolerance is achieved and the full dose can be administered safely. This is a dangerous procedure, but if the health risks of the disease outweigh the allergy, it may be necessary.

Latex protein from the rubber tree has many uses, especially in the medical environment. Latex allergy affects about ten per cent of healthcare workers and can cause allergic conjunctivitis, contact dermatitis, hives, allergic rhinitis, asthma and even anaphylaxis within minutes of exposure.

Reactions may occur when blowing up a balloon or wearing rubber gloves or even using a latex condom. Latex can also be found in rubber handles, shoes, baby bottle nipples, dummies, clothing elastic and a host of medical equipment.

Some people are so highly sensitive to latex they develop allergies to latex-related foods, such as avocado, kiwi, banana and chestnuts.

Testing can be done by RAST, skin-prick and challenge tests. There are a number of alternative latex-free products such as neoprene, vinyl and plastic, and latex is slowly being phased out of rubberised goods.

If you have a latex allergy, make sure you inform your GP, dentist and surgeon and wear a MedicAlert bracelet.

In certain genetically predisposed people, aspirin (salicylate) and related non-steroidal anti-inflammatory medications (ibuprofen, diclofenac, mefenamic acid and indometacin) cause allergy-like reactions by blocking a certain metabolic pathway in the body.

This leads to an excessive production of leukotriene inflammatory chemicals in the blood. These leukotrienes can trigger asthma attacks in adults, cause urticaria and angioedema swelling, and encourage the growth of nasal polyps that block the nose and cause chronic rhinitis.

About 20 per cent of asthmatic adults are sensitive to aspirin (otherwise known as salicylate). Dietary salicylate naturally occurs in berry fruits, spices and strong tea, and if taken in excess may aggravate symptoms in salicylate-sensitive people.

This article was last medically reviewed by Dr Adrian Morris in September 2007.
First published in September 1999.

Thanks to Royal Brompton & Harefield NHS Trust for allowing BBC Health to take photos.