Ibuprofen is a popular drug from the class of non-steroidal anti-inflammatory drugs (NSAIDs). Ibuprofen is indicated for use as an analgesic (pain reliever) and antipyretic (fever reducer). It is also approved as an anti-inflammatory agent and is prescribed in arthritic conditions such as osteoarthritis, and rheumatoid arthritis, and debilitating musculoskeletal disorders.

Image Credit: Michelle Lee Photography / Shutterstock.com

Mechanism of action of ibuprofen

Non-steroidal anti-inflammatory drugs such as ibuprofen are inhibitors of the enzymes cyclooxygenase (COX-1) and cyclooxygenase (COX-2). The COX enzymes play a pivotal role in the synthesis of prostanoids, such as thromboxane, prostaglandins, and prostacyclin, from arachidonic acid. COX1 produced prostanoids are important in regulating kidney function, platelet aggregation, and integrity of the gastric mucosa; COX2-generated prostanoids are essential for inflammation.

Ibuprofen binds reversibly to the COX 1 and COX 2 receptors and inhibits arachidonic acid from binding to these receptor sites. This mechanism prevents the conversion of arachidonic acid to the various inflammatory prostaglandins. Prostaglandins also sensitize the pain-sensing nerves, which accounts for the pain-relieving effect of ibuprofen.

Even though ibuprofen is a therapeutically useful drug, frequent use of ibuprofen has been linked to adverse reactions, ranging from mild skin rashes or gastric problems to severe, life-threatening hypersensitivity reactions such as anaphylaxis.

Hypersensitivity reactions related to NSAIDs may be due to immunological or non-immunological mechanisms.  Hypersensitivity reactions to NSAIDs are poorly characterized, and the heterogeneous nature of clinical symptoms makes it difficult to detect diagnosis and treat.

What are the symptoms of ibuprofen allergy?

Ibuprofen use may lead to a severe allergic reaction and is most common among those with an allergy to aspirin.  Ibuprofen-related allergic reactions may be either immunoglobin E (IgE)-mediated or non-IgE mediated. Symptoms of ibuprofen allergy may include the following:

·Hives

·Facial swelling

·Rash

·Asthma (wheezing)

·Difficulty breathing

·Shock

·Skin reddening

·Blister

How is ibuprofen allergy diagnosed?

The diagnosis of ibuprofen allergy is a challenging task. There are no reliable in vitro confirmatory tests; the presence of clinical variability in the observed reactions further adds to the problem.

As allergy may be caused by many different reasons, differential diagnosis plays a key role in detecting and confirming ibuprofen allergy. A skin prick test may be conducted to rule out other potential causes of allergy, such as food, latex, insect stings, venom, etc. Blood tests may also be used to detect if the body is predisposed to an allergy to certain substances.

Skin tests may include patch tests, skin prick tests, and intracutaneous tests.

• A patch test is used to diagnose contact allergies. A patch test involves placing the allergens into test chambers. This patch is then placed in direct contact with the skin with the help of an adhesive tape.
• A skin prick test may be used to detect for immediate-type allergies. In this test, extracts of suspected allergens are applied with the help of a dropper to the skin, and the skin is then pricked with a small blade. The results are confirmed by evaluating the redness on the skin. Prick-to-Prick test is similar to a simple skin prick test; however, real food is used instead of commercial allergens.
• An intracutaneous test involves injecting the allergen solution into the surface of the skin, while, in the rub test, the suspected allergen is rubbed on the skin or applied to the skin.

Blood tests can be conducted to determine the levels of IgE and IgG antibodies in the blood, which can be helpful in determining whether a patient may be experiencing an allergy to a substance.

When skin tests and blood test fail to detect the cause, the only effective way to establish the diagnosis is via a provocative challenge test. In the provocative challenge test, the suspected allergen is administered to the patient in minute quantity, and the patient is then observed for any physical reaction. Provocation tests can be conducted as an oral provocation test, nasal provocation test, or inhalation provocation test. These tests are only performed in medical settings in which immediate emergency intervention can be provided if a severe reaction occurs.

Family history must be checked to the possibility of genetic diseases such as hereditary angioedema, which resembles allergy in symptoms but is caused by a genetic mutation.

The doctor may link the onset of allergy with the duration of ibuprofen exposure. The doctor may also check if avoiding ibuprofen for a certain period of time leads to a complete absence of allergic episodes to confirm the diagnosis.

How is ibuprofen allergy treated?

Strict avoidance of ibuprofen is the only management strategy that can be used in patients with ibuprofen allergy. Care must be taken in using other NSAIDs, as patients may also be allergic to aspirin or other drugs within this class. Acetaminophen is an analgesic that is unrelated to NSAIDs and might be a good alternative for minor pain or fever in patients who cannot take ibuprofen.

Sources

• Ershad M, Vearrier D. Ibuprofen Toxicity. [Updated 2019 Jun 16]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526078/
• Kay, E., & Ben-Shoshan, M. (2013). Anaphylaxis to ibuprofen in a 12-year-old boy. BMJ case reports, 2013, bcr2012007873. doi:10.1136/bcr-2012-007873
• Ibuprofen Drug Facts Label. 2016. USFDA. Available at: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/ibuprofen-drug-facts-label
• Allergy Tests Overview. European Centre for Allergy Research Foundation. Available at: https://www.ecarf.org/en/information-portal/general-allergy-info/allergy-tests-overview/

Further Reading

• All Ibuprofen Content
• What is Ibuprofen?
• Ibuprofen Chemistry
• Ibuprofen Mechanism
• Ibuprofen Side Effects