Supplementary memorandum by Dr Richard
Pumphrey, Consultant Immunologist, St Mary's Hospital, Manchester
At the meeting on 31 January, Baroness Finlay
of Llandaff asked me to prepare a brief written statement about
the investigation and treatment of drug allergy.
Almost every drug has caused adverse effects
in a proportion of those being treated. The range of these effects
is wide and the underlying mechanisms varied and often poorly
understood. When the drug reaction is due to hypersensitivity,
this may be non-allergic or allergic, and if allergic, may be
IgE-mediated[20]
or non-IgE-mediated.
IGE-MEDIATED
DRUG ALLERGY
This type of reaction characteristically causes
rapid development of symptoms after exposure to the drug, commonly
including rashes or swellings but in more severe cases involving
shock or difficulty breathing. Tests for this type of allergy
are based on the binding of the drug to IgE in a specimen of the
patient's serum, or by challenge with a small quantity of the
drug by skin prick test. More reliable but potentially dangerous
is a drug challenge (drug provocation) test, when the patient
is given a dose of the suspected drug under conditions where it
is hoped the adverse effect will be limited and the patient can
be rescued from any reaction that occurs.
The most severe form of IgE-mediated allergy
is termed anaphylaxis. In the UK around 10 deaths are attributed
to drug anaphylaxis each year.
NON-IGE-MEDIATED
DRUG ALLERGY
Many different processes are lumped together
under this heading, previously grouped as type II, type III and
type IV hypersensitivity. Some can be tested in the laboratory,
some by skin tests, some by microscopic examination of biopsies.
Some mechanisms thought to occur in humans by extrapolation from
the results of animal experimentation cannot yet be routinely
investigated in the clinic or laboratory.
The most severe forms of non-IgE-mediated drug
allergy include a group of related conditions known as Stevens
Johnson Syndrome and Toxic Epidermal Necrolysis. A few patients
die from these conditions each year.
The least severe reactions include drug rashes:
these are very common and mostly cause problems because they are
thought to signify the potential for a more serious reaction if
the patient is given that drug again, leading to future treatment
with more expensive and sometimes less effective or less safe
alternative drugs. Unfortunately we do not have reliable tests
that will allow us to assess the risk of a recurrence of the reaction,
though in most cases it is probably rather low.
NON-ALLERGIC
DRUG HYPERSENSITIVITY
Many different processes fall into this category.
For example, angiotensin converting enzyme (ACE) inhibitors are
widely used for treatment of blood pressure. These are good effective
drugs but cause side effects in a small subset of those taking
them, for example swellings that may be fatal if they occur in
the throat and block the airway. The mechanism for this is known
in considerable detail and there is potential for simple tests
to predict who might be affected—however, in practice the
drug is given to anyone who might benefit and those who react
are then changed to an alternative treatment; this approach results
in one or two deaths each year. Many other examples could be given,
often dependent on single gene differences affecting the metabolism
of the drug or the structure of receptors that can bind to it.
TREATING DRUG
ALLERGY
Although much is understood of the principles
of different drug reactions, it is usually difficult in any individual
case to be sure that which mechanism is truly the cause of the
reaction. The usual management is to avoid the suspected drugs
in future and use alternatives that are thought to pose less of
a risk. Often one has to balance the risk of avoiding the suspect
drug against the risk of using it despite the suspicions that
it may have caused a reaction.
A particular set of problems is caused by reactions
during anaesthesia. Most of the fatal drug reactions are of this
type and have been thought to be due to muscle relaxants, opiates
or antibiotics. One difficulty is due to modern anaesthetic techniques
where multiple drugs are given in quick succession at induction
of anaesthesia; this can make it difficult to identify which drug
was to blame. Further research is needed to improve the sensitivity
and specificity of the tests used to investigate such reactions.
SPECIALIST CLINICS
FOR DRUG
REACTIONS
This brief synopsis should make clear the difficulties
faced by those who have reacted to a drug. They are unlikely to
get ideal advice from any but the best informed of specialist
clinics. I recently undertook a survey of the majority of UK clinics
offering this type of testing. The variety of approaches and heterogeneity
of findings suggests the need for further research into the most
effective approaches and guidance for such clinics to raise the
standard of all to that of the best.
20 IgE is the abbreviation for immunoglobulin E, the
class of antibodies involved in triggering immediate-type allergic
responses. Back
| 
