2018 Oral Provocation Test in Non-Steroidal Anti-Inflammatory Drug Hypersensitive Patients Referred to Singapore General Hospital

Thursday, 15 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Tze Chin Tan, MD, MRCP(UK) , Singapore General Hospital, Singapore, Singapore

Yong Yeow Chong, MBBS(Sípore), MRCP(UK), MMed(Int Med), FAMS , Singapore General Hospital, Singapore, Singapore

Chaw Su Naing, MBBS, MRCP(UK), MSc Allergy(UK) , Internal Medicine, Singapore General Hospital, Singapore, Singapore


Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed classes of drugs and are easily accessible as over-the-counter anti-inflammatory drugs in Singapore. NSAIDs hypersensitivity is the second most common referral to allergy clinic in a tertiary referral centre.


Referred patients with history of NSAID-induced urticarial, angioedema or anaphylaxis underwent open challenge with (1) putative NSAID to confirm the diagnosis; (2) Aspirin to determine the cross-reactivity or (3) selective cyclooxygenase-2 (COX-2) inhibitor to identify the suitable alternative. Data were analysed retrospectively.


Over a 4-year period (2010-2014), 127 patients with mean +/- SD age, 40.7 +/- 15.2 year, underwent a total of 155 open-labelled labelled NSAIDs oral provocation tests (OPT). Patients demographics consisted of female (63.8%, 81) with majority Chinese ethnic group (80.3%, 102). Diclofenac (20.2%) and Naproxen (19.7%) were the two commonest reported culprits NSAIDs.  In 32 (25.2%) patients, more than 2 eliciting NSAIDs were recorded to cause hypersensitivity reactions. However, 27 (21.3%) patients reported to tolerate different groups of NSAIDs and 40 (31.5%) had concomitant intolerance to Acetaminophen. Urticaria and/or angioedema were the most frequently reported symptom (87.3%), among which 60.6% were isolated periorbital angioedema. Reaction involving the airways i.e., asthma with or without a naso-occular symptoms were rare (7%). Anaphylaxis was reported by 4(3.1%) patients together with other concomitant drugs.

Breakdown for 155 challenges was as follows: 68 (43.9%) Putative NSAIDS challenge, 29 (18.7%) Aspirin challenge and 58 (37.4%) selective COX-2 inhibitor challenge.  Overall positive challenge rate was 24.5% (38 out of 155). Despite having a clinical relevant history of causative, only 29.4% (20 out of 68) had positive OPT to putative NSAIDs. Aspirin challenge resulted in 48.3% (14 out of 29) positive challenge, hence confirming the diagnosis of NSAIDS intolerance. Using selective COX-2 inhibitor challenge, we found only 6.9% (4 out of 54) positive challenge. For the anaphylaxis cases, cautious OPT with putative NSAIDS were done in 75% (3 out of 4) patients. No reaction was found.


Without validated skin test, OPT helps evaluate NSAIDS hypersensitivity patients. Our 4-year patients cohort with a positive OPT rate of 24.5% confirmed diagnosis of NSAIDs hypersensitivity. With low positive OPT rate of 6.9%, selective COX-2 inhibitor can be used as alternative in these patients.