NSAI (ASA-Aspirin) Sensitivity / Reactions

NSAIs (nonsteroidal anti-inflammatories) comprise a rather large group of medications. The initial prototype was ASA. Some of these medications are listed just so individuals can identify one or more that they may have taken : ibuprofen (Motrin TM, Advil TM), diclofenac(Voltaren TM), Etodolac, indomethacin (Indocid TM), ketorolac, sulindac, celecoxib (Celebrex TM), meloxicam, piroxicam, ketoprofen, naproxen, naproxen sodium, diflunisal, nabumetone, and others. NSAIs share molecular similarities and all produce a combination of analgesic and anti-inflammatory effects. Some possess some more analgesic and/or anti-inflammatory effect than others. Some are more closely related to ASA than others. Reactions to NSAIs can start at any age and it is not unusual that once you react to one NSAI you can have similar reactions to some of the others in the future (but, there is no guarantee that this will occur). When an individual reacts to one NSAI avoidance of the entire group is often recommended unless another in the group is being used and is known to cause no reaction.

The Reaction Itself

Reactions to NSAIs can be subdivided into: A-skin only (itching, rash, hives, swelling (angioedema); B-respiratory (nose, sinuses, chest-wheezing (acute asthma), coughing, difficulty breathing; C- multisystem reactions which can include skin, respiratory, bowel, cardiovascular (low blood pressure /shock /anaphylaxis).

For the purposes of our discussion is more useful to look at reactions to NSAIs in terms of their severity. Mild reactions involving the skin are not as serious as reactions involving the respiratory or cardiovascular systems. Not only can these reactions vary in the systems that they affect, but the severity of reactions can be highly variable between individuals. For example a single 325 mg aspirin may cause simply itching in one individual where the same dose could cause severe hives-generalized swelling-low blood pressure in another individual. The bottom line is that the type of reaction can vary from one individual to another as can the severity of a specific reaction.

The Reaction Mechanism

This is an extremely important concept that any individual with NSAI sensitivity must understand. The reactions that are listed above are typical of true allergic reactions. True allergic reactions are mediated by the immune system and usually IgE antibodies (please go back to The Contents Section to review in more detail a true allergic reaction). Nonsteroidal anti-inflammatories usually have a direct chemical effect on the cells/mediators that cause allergic reactions and this reaction is not usually mediated via the immune system. This is critical as this means most NSAI reactions are dose dependent. For example, an individual who is ASA sensitive may get only slight itching from a baby aspirin (81 mg) or perhaps no reaction at all, where a dose of 325 mg would cause severe itching, and a dose of 650 mg would cause severe hives and swelling (angioedema). This is merely an example, keeping in mind that every individual has their own level of sensitivity. There are individuals who are severely sensitive and even a small dose of a nonsteroidal anti-inflammatory can cause anaphylaxis. On the other hand I have multiple patients who can take one standard ibuprofen 200 mg with no problem and yet get itchy-hives if they take two ibuprofen 400 mg. ASA (aspirin) in low dose (81 mg) is used extensively in the treatment and prevention of heart disease and stroke. If an individual taking low-dose aspirin has a history of a reaction to another NSAI it should not be automatically assumed they can tolerate higher doses of aspirin. The bottom line is NSAI reactions are dose dependent with each individual having their own level of sensitivity (severity of reaction).

Practical Aspects of NSAI Sensitivity

1-Allergy testing for NSAI sensitivity is usually negative (because, as I explained above it is not a true allergic reaction so allergy tests are negative).

2-The only way to confirm NSAI sensitivity is for the individual to take the nonsteroidal anti-inflammatory (almost always by mouth) and have a reaction.

3-Because individuals with NSAI sensitivity can react to more than one NSAI, usually avoidance of the entire group is recommended once the diagnosis is made.

4-If an individual who is NSAI sensitive tries a different NSAI (oral challenge procedure) the initial dose should be extremely small (because this is a dose-dependent reaction). Most oral reactions to NSAIs occur within half an hour so the dose can gradually be increased every half-hour until reaching standard dose or a reaction occurs. By starting with an extremely low dose we want to keep any reaction as mild as possible.

5-There is tremendous variation in individual sensitivity to nonsteroidals, and anyone with a history of a serious or severe reaction to a previous nonsteroidal requires any oral challenge to be done in a medical facility with appropriate medical supervision, monitoring, and resuscitation equipment at hand. These individuals need a Medic Alert TM bracelet/pendant/etc. stating: NSAI Sensitive – severe.

6-Many individuals who are NSAI sensitive simply avoid all members of this group. However, as these individuals get older and develop cardiovascular disease it is often recommended that they go on low-dose ASA-aspirin 81 mg. This decision must be made by a fully informed patient regarding NSAI sensitivity. For example, an individual with a history of a very mild reaction to 400 mg of ibuprofen may be quite willing to try a small dose of a baby aspirin (i.e. 20 mg, one quarter of an 81 mg tablet) and increase by one quarter tablet-20 mg every half-hour until they reach 81 mg at home on their own (continuing on with 81 mg if they are fine). This approach requires a very clear-cut accurate history of previous reaction(s), a fully informed physician and patient, and a patient who is willing and capable of doing this at home. The more vague the story of a previous NSAI reaction or the more severe the previous reaction the more you should consider having any possible NSAI challenge appropriately conducted by medical personnel.

If you have a history of a reaction or possible reaction to a NSAI discuss this with your doctor (if you have not done so already).

Bruce Sweet MD 2012