What is aspirin used for?
Aspirin has long been used to reduce pain from inflammation
and injury, as well as fever. Originally isolated from Willow
Tree Bark and other plants in the early 1800's, natural salicylates
were found to be effective for the treatment of pain and fever.
Unfortunately, these products were very irritating to the stomach.
The preparation of salicylic acid salts such as acetyl salicylic
acid (aspirin) were found to be just as effective but with less
side-effects. These days, aspirin is made synthetically, and a
number of similar synthetic non-steroidal anti-inflammatory drugs
(NSAIDS), have been introduced.
How do aspirin and NSAIDS work?
Compounds known as prostaglandins play an important role in
tissue inflammation, pain and fever. Production of prostaglandins
is inhibited by aspirin and related medications (NSAIDS), because
these medications inhibit an enzyme known as cyclooxygenase-1,
(COX-I). Because aspirin also inhibits the activity of blood elements
known as platelets (which help clotting), aspirin also thins the
blood, thus reducing the risk of heart attacks and strokes. There
is also recent evidence that aspirin may reduce the risk of bowel
cancer as well.
All drugs are potential poisons; aspirin is no exception
Common side effects include bruising and stomach upset (or
even ulcers or bleeding from the bowel), at high dose. Very high
doses may cause confusion and ringing in the ears (tinnitus).
It should also be avoided in children, as aspirin can trigger
a condition as Reye's syndrome, where severe liver inflammation
and damage may occur.
Aspirin and allergy
Mild to severe allergic reactions to aspirin may occur. When
assessing reactions to aspirin and similar medications, it is
useful to look for evidence of underlying disease such as hives
(urticaria), nasal / sinus disease, or asthma. This is because
the presence of underlying medical conditions may make it more
likely that an individual may react to aspirin or similar drug.
How common is aspirin allergy?
TYPES OF ASPIRIN ALLERGY
When assessing reactions to aspirin and similar medications, it
is useful to look for evidence of underlying disease such as hives
(urticaria), nasal / sinus disease, or asthma. This is because
the presence of underlying medical conditions may make it more
likely that an individual may react to aspirin or a similar medication.
1. Aspirin sensitivity in patients
with underlying hives / urticaria
In patients with ongoing hives/urticaria,
aspirin and NSAID may result in a severe flare of symptoms within
a few hours in a third of patients. Sensitivity to aspirin / NSAIDS
usually disappears when symptoms of hives improve. This suggests
that these medicines increase the irritability of the skin, and
that patients are not actually allergic to the drug itself. Patients
with on-going hives who are either already taking aspirin to thin
the blood, or a regular pain killer for treatment of arthritis,
do not need to stop their medication.
2. Allergic reactions to aspirin /
NSAIDS
Allergic reactions to aspirin and related medicines
can occur in the absence of underlying disease such as hives/urticaria
or asthma/rhinitis/nasal polyps. The symptoms are hives and swelling
and sometimes worse symptoms (such as anaphylaxis),
may occur within a few hours of taking aspirin or a related drug.
These reactions are unpredictable, and occur within a few hours
of taking the tablet. Whilst most of those affected will be sensitive
to only one anti-inflammatory medicine, up to 20 per cent have
similar reactions to other anti-inflammatory drugs/NSAIDS. Such
"cross-reactions" are also unpredictable, and do not
appear to relate either to the chemical structure (shape) of the
medicine, or its ability to inhibit COX-I enzymes.
3. Aspirin sensitive asthma/rhinitis/sinusitis/nasal
polyps
Known as the "aspirin triad" (Samter's Triad),
this inflammatory condition affects the upper and lower airways.
There are actually four features to this condition, consisting
of a blocked and drippy nose (rhinitis), nasal
polyps, asthma (often of late onset), and aspirin sensitivity.
These symptoms can develop slowly over several decades, with asthma
and aspirin sensitivity developing last. Many patients are not
allergic to inhaled allergen such as dust mite, grass pollens,
moulds or animal danders.
Patients with this condition often have asthma that is more difficult to treat than average, with higher doses of medicines required. Nasal polyps often return soon after surgery to remove them, and many patients suffer from recurrent sinus infections and poor sense of smell and taste.
These patients have an increased production of inflammatory chemicals known as leucotrienes. Leucotrienes are produced by tissue leucocytes (white cells). These attract more white cells into the tissues, thus increasing inflammation. Leucotrienes also cause swelling, mucous production, spasm of muscle in the airways and worsen asthma. Patients with this condition have an increased baseline production of leucotrienes and increased expression of leucotriene receptors in various tissues. The severity of their symptoms can often be improved by either using a medication to bloc the action of leucotrienes (eg. Singulair / montelukast), or aspirin desensitization (see below) to reduce the production of leucotrienes.
When they take aspirin or a related NSAID, inhibition of the COX-I enzyme results in reduced production of protective prostaglandins. This results in acute asthma, blocked and runny nose as well as facial flushing within a couple of hours. Occasional patients with the Aspirin triad will also be sensitive to paracetamol (Panadol, Heron), particularly when high doses of 1gm or more (2 tablets), are used.
4. Patients with anaphylaxis / severe
allergy of other causes
Even when patients are not allergic to aspirin or pain-killers,
taking aspirin on the same day as food allergen can increase the
likelihood that an allergic reaction may occur, and increase its
severity. It is currently thought that taking a pain killer may
cause the stomach/bowel to be more "leaky", increasing
the rate of absorption of food allergen, and thus making an allergic
reaction to food more likely.
5. Uncommon reactions: pneumonitis
due to NSAIDS
Occasional patients will develop severe lung inflammation
known as hypersensitivity pneumonitis, after taking some NSAIDS.
These reactions are rare, usually occur with one drug only, and
disappear when the medicine is withdrawn.
The presence of aspirin is not always obvious
Aspirin is present in many across-the-counter pain-killers
as well as various sinus, period pain or cold & flu tablets.
Patients with aspirin sensitivity need to be warned to carefully
read labels and to be wary of taking any pain-killer without consulting
their doctor or pharmacist first.
There are many brands of NSAIDS
Because there are so many brand names of the same medication,
and so many types of medications available, accidental exposure
to NSAIDS may occur. It is therefore important to tell your pharmacist
or health professional about your sensitivity to these medicines.
Testing for drug sensitivity
The mechanism by which allergic reactions to aspirin and related
pain-killers occur is uncertain. When such reactions do occur
however, they appear to be independent of IgE. The implication
is that there is no reliable blood or skin allergy test which
has been proven to be useful in either confirming or excluding
drug sensitivity to these compounds. The only way to do so is
to do a graded open challenge under strict medical supervision.
Appropriate resuscitation facilities need to be available, as
reactions can be severe and potentially dangerous. Challenge testing
is therefore generally performed for one of two reasons. The first
is to prove that sensitivity exists. The second is to prove the
safety of an unrelated medicine, so
What is aspirin desensitisation?
This is useful in selected patients with the "aspirin
triad". The average aspirin tablet contains 300 mg of aspirin.
By starting off at a very low dose of aspirin (e.g. 1 5
mg/day) initially, one can slowly increase the dose of aspirin
so that the patient can tolerate it. When a higher dose is reached
(between 1 4 tablets/day), there is reduced production of
leucotrienes, reduced expression of leucotriene receptors in the
tissues, and clinical benefit follows. Aspirin desensitisation
has been shown to reduce the severity of asthma and need for asthma
medication, to reduce the rate of polyp regrowth, and to reduce
the severity of sinusitis. Aspirin desensitisation can be performed
as an in-patient or out-patient, but that decision is best made
by an allergy specialist.
Side-effects of aspirin desensitisation
Gut Irritation ulceration and bleeding at high doses
Easy bruising - common
Tinnitus (ringing in the ears rare)
Reasons for undertaking aspirin desensitisation
Management of aspirin / NSAID sensitivity
Ongoing hives
Patients who have on-going hives/urticaria should avoid aspirin
and NSAIDS unless they know that they can tolerate them without
a problem. If they are already taking regular aspirin (for example,
to thin the blood), or a regular arthritis tablet for treatment
of pain, then they do not need to stop this medicine unless their
hives clearly get much worse after taking a tablet. "aspirin
desensitisation" has been attempted in patients with chronic
urticaria, but is not effective in the majority of cases.
Acute hives/anaphylaxis
While most patients are sensitive to one drug only, an estimated
1:5 may have unpredictable cross-reactive allergic responses to
similar medicines. Under these circumstances, an open challenge
with a completely different drug can be considered if the patient
needs to take a pain killer for treatment of chronic pain states
or arthritis.
Aspirin Sensitive Asthma/Nasal Polyps/Sinusitis/Rhinitis
Leucotriene antagonists (such as Singulair / montelukast) or aspirin
desensitisation (see above) are useful treatment options.
Tolerability of new COX-II inhibitors
A number of new medicines have been introduced in the last
few years, which inhibit an enzyme known as Cyclooxygenase II
(COX-II). Many of these drugs (eg. Celebrex, Vioxx) have some
inhibitory reaction on COX-I as well. Whilst they cause less stomach
irritation than aspirin and traditional NSAIDS, some patients
will have allergic reactions to these as well. Published estimates
are of the order of 5 to 20 %.
Dietary salicylates in aspirin-sensitive patients
Occasional patients who are allergic to aspirin, and have
the "aspirin triad", will suffer symptoms if they eat
foods that have high levels of naturally occurring salicylates.
This affects the occasional patient rather than the majority,
and so low salicylate diets are not considered a routine part
of management.
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