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Journal of Postgraduate Medicine, Vol. 56, No. 1, January-March, 2010, pp. 36-37 Case Snippet Immediate hypersensitivity reaction to a single oral dose of flurbiprofen Mehra KK, Rupawala AH, Gogtay NJ Department of Clinical Pharmacology, 1st Floor, MS Building, Seth GS Medical College and KEM Hospital, Parel, Mumbai - 400 012, India Correspondence Address: Dr. Nithya J. Gogtay, Department of Clinical Pharmacology, 1st Floor, MS Building, Seth GS Medical College and KEM Hospital, Parel, Mumbai - 400 012, India, njgogtay@hotmail.com Code Number: jp10012 PMID: 20393250 DOI: 10.4103/0022-3859.62429 Flurbiprofen is a prostaglandin-synthetase inhibitor with anti-inflammatory activity. It has been approved by the United States Food and Drug Administration (US FDA) in 1988 for the treatment of rheumatoid arthritis and osteoarthritis. Like other non-steroidal anti-inflammatory drugs (NSAIDs) of its class, flurbiprofen is commonly associated with side-effects related to the gastrointestinal and renal system. Other side-effects reported include contact dermatitis, [1] delayed hypersensitivity, cutaneous vasculitis, cholestasis. [2] In this report we describe a hypersensitivity reaction to a single, oral dose of flurbiprofen in an individual with a prior history of immediate hypersensitivity to an oral dose of ibuprofen. A 28-year-old male presented with swelling around the eyes associated with redness and increased lacrimation occurring 20 minutes after ingesting 100 mg of flurbiprofen as a part of a research study [Figure - 1]. The symptoms were preceded by itching of both the eye globes and eyelids. There were no complaints of any rash elsewhere in the body or respiratory symptoms like wheezing, chest tightness and difficulty breathing. He gave history of a similar reaction to an oral dose of ibuprofen within a similar time frame, two years prior. This information was not mentioned to the investigator during recruitment for the study. He had no history of previous exposure to flurbiprofen or any other drug or food allergy. He was treated by his primary care physician with oral anti-histaminic chlorpheniramine maleate (4 mg) and oral corticosteroid dexamethasone (0.25 mg) both given thrice a day for three days. The swelling subsided within two days. On the Naranjo′s causality assessment scale, the adverse event was assessed to be probably causally related to flurbiprofen (Score 7). [3] NSAIDs are a chemically heterogeneous group of compounds, known to cause a wide variety of cutaneous reactions. Some authors believe that these wide varieties of reactions indicate that diverse mechanisms may be responsible. It is postulated that since NSAIDs affect the inflammatory pathway, many of the observed cutaneous effects of these drugs result from alteration of this pathway rather than from classic hypersensitivity reactions. [4] However, there is some evidence suggesting that rashes may be manifestations of type IV hypersensitivity. [2] There is also evidence in the literature of an IgE-mediated reaction to ibuprofen leading to aseptic meningitis. [5] There is evidence showing cross-reactivity between flurbiprofen and ibuprofen, ketoprofen and tiaprofenic acid, [1] suggesting common antigenic determinants. Higher frequency of allergic reaction to propionic acid derivatives as compared to other NSAIDs is also known which indicates a probable class effect. [6] To confirm the causal relationship, pathogenesis and cross-reactivity in this case it would be imperative to do a patch test using both ibuprofen and flurbirofen. However, due to the risk of anaphylaxis, it has to be done in the Medical Intensive Care Unit for which the participant did not consent. The other test that could be done, but was not done in this case is the Basophil Activation Test [7] - an in vitro diagnostic test to detect hypersensitivity and serum IgE levels. Thus, the reaction could be anaphylactic or anaphylactoid in nature. However, an IgE-mediated hypersensitivity mechanism is suggested by the rapid onset of reaction, and the previous reaction to ibuprofen suggests a cross-reactivity with flurbiprofen. Flurbiprofen is used orally for analgesia in several countries and is also a component in ophthalmic solutions. Hence, it would help clinicians to be aware of allergy to flurbiprofen and its cross-reactivity with other propionic acid group NSAIDs. References
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