Identifying true drug allergies

-nzdoctor.co.nz

12/05/2007 - Adverse drug reactions may be immune mediated or recognised side effects of the drug. Immune-mediated responses involve immunogobulins; the complement system; immune complexes and cell-mediated T cell responses. Side effects include recognised side effects of the drug; interactions with other drugs; and overdoses (accidental, deliberate or too large a dose).

The main drug allergens include analgesics, antibiotics, anticonvulsants and anaesthetics. Penicillin allergy kills more people each year than peanut allergy, yet the latter currently receives much more attention and column inches in the press.

Risk factors in the host include being elderly and female; being ill with an infection; being immunocompromised; and having renal and/or hepatic disease. Interestingly, a family history of adverse drug reactions (ADR) is not helpful and there are no data to support children being more at risk of an ADR due to a parent experiencing an ADR. The method of drug delivery can also affect the risk of an ADR. These factors are generally intuitive: intravenous drug delivery is more likely to cause an ADR than oral drug delivery; high doses and multiple doses of the drug are riskier than low doses and single or few doses respectively; high molecular weight drugs are also riskier than low molecular weight drugs.

A careful history is needed to establish the symptoms thought to have indicated an ADR. One of the most common is the development of a rash after starting to take the drug. Details of the rash are important, as an urticarial rash is more commonly associated with an ADR than a macular papular rash, which is more commonly associated with an illness. Other features can include a drug fever or organ-specific symptoms, such as abnormal liver or renal function. Investigations can include IgE immunoglobulins; however, these have variable sensitivity and specificity even if immunoglobulin tests are available for a specific drug. In vivo tests include skin-prick testing and patch testing.

The gold standard is to rechallenge the patient with the drug. The difficulty with this approach is, when dealing with a child, the parents are understandably reluctant to expose their child to a perceived risk, if they believe the particular drug was responsible for the ADR. Also, when the patient is rechallenged they are usually well, so are probably not in an equivalent immunological state to when the drug was first taken (assuming they were ill when it was first taken). However, it can be important to establish the veracity or otherwise of the ADR or the patient may be condemned to an unnecessary lifelong avoidance of a particular medication. The belief they have an ADR may then pass down through the generations when they have children and become a family myth – “We have penicillin allergy in our family.” The question is whether the patient is “allergic to” or “tolerant to” a particular drug.

Options include avoiding the same drug and any cross-reacting agent; for example, people who are allergic to penicillin are usually advised to avoid cephalosporins. However, the cross reactivity between the two is reported as being around 3 to 8 per cent, which is not much higher than the overall population risk for being allergic to cephalosporins. Is there an alternative drug that can be used, eg, a totally different type of antibiotic? Can the patient have a provocative dose challenge, usually in hospital? If the patient has had a very severe ADR, such as Stevens-Johnson syndrome, then both the patient and the doctor would be understandably loath to do this.

Can the patient be desensitised or at least tolerance induced? This can either be done by a slow graded introduction of the drug or by rush desensitisation. Rush desensitisation has a precedent; eg, wasp venom can be given by six injections over a very short space of time leading to desensitisation to wasp stings.

The question has to be asked as to whether a reaction was a drug allergy and, if so, to which allergen? A common example of this is an ADR where a patient is given a local anaesthetic in a dental surgery. There can be many factors, such as latex in the dentist’s gloves; antibiotics if the patient has an abscess; drugs containing adrenalin; whether the patient is anxious; and whether there is contact with mucous membranes. This could have been a vasovagal attack in which the pulse rate gets slower, as opposed to anaphylaxis in which the pulse rate is more likely to increase – the two are very different conditions.

KEY POINTS

• Main drug allergens include analgesics, antibiotics, anticonvulsants and anaesthetics.
• A family history of adverse drug reaction (ADR) is not helpful and there are no data to support children being more at risk of an ADR due to a parent experiencing an ADR.
• A common symptom of an ADR is the development of a rash. An urticarial rash is more commonly associated with an ADR than a macular papular rash (more commonly associated with an illness).
• Other features of an ADR can include a drug fever or organ-specific symptoms, such as abnormal liver or renal function.
• Rechallenging the patient with the drug is preferable, though parents may be reluctant to do this for a child.
• Options include avoiding the same drug and any cross-reacting agent; trying a different type of drug; and considering desensitisation or “tolerance” treatment.

Ennis & Ennis, P.A. is representing individuals that have Stevens Johnson Syndrome due to side effects of prescription drugs. For more information about a Steven's Johnson Syndrome related lawsuit click here to contact our lawyers for a free, confidential case evaluation.