Early Presentation With Angioedema and Urticaria in Cross-reactive Hypersensitivity to Nonsteroidal Antiinflammatory Drugs Among Young, Asian, Atopic Children

Abstract

ABSTRACT. Objective. Nonsteroidal antiinflammatory drugs (NSAIDs), mainly ibuprofen, are used extensively among children as analgesic and antipyretic agents. Our initial survey in the Kendang Kerbau Children's Hospital in Singapore showed NSAIDs to be the second most common adverse drug reaction-causing medications among children of Asian descent. We attempted to characterize the clinical and epidemiologic profile of NSAID reactions in this group of patients.Methods. A retrospective case series from a hospitalbased pediatric drug allergy clinic was studied. A diagnosis of NSAID hypersensitivity was made with a modified oral provocation test. Atopy was evaluated clinically and tested with a standard panel of skin-prick tests. We excluded from analysis patients with any unprovoked episodes of urticaria and/or angioedema, patients <1 year of age, and patients who refused a diagnostic challenge test.Results. Between March 1, 2003, and February 28, 2004, 24 patients, including 14 male patients (58%) and 18 Chinese patients (75%), with a mean age of 7.4 years (range: 1.4 -14.4 years), were diagnosed as having crossreactive NSAID hypersensitivity. A family history consistent with NSAID hypersensitivity was elicited for 17% of patients. None of the patients reported any episodes of angioedema/urticaria unrelated to NSAIDs. The median cumulative reaction-eliciting dose was 7.1 mg/kg. Facial angioedema developed for all patients (100%) and generalized urticaria for 38% of challenged patients, irrespective of age. There was no circulatory compromise, but respiratory symptoms of tachypnea, wheezing, and/or cough were documented for 42% of patients. A cross-reactive hypersensitivity response to acetaminophen was documented for 46% of our patients through their history and for 25% through diagnostic challenge. Compared with patients with suspected adverse drug reactions to antibiotics, patients in the NSAID group were older (7.4 vs 4.8 years) and more likely to have a diagnosis of asthma (odds ratio: 7.5; 95% confidence interval: 3.1-19).Conclusions. Early presentations of facial angioedema and urticaria are key features of dose-and potency-dependent, cross-reactive reactions to NSAIDs in a subpopulation of young, Asian, atopic children. Significant overlap with acetaminophen hypersensitivity, especially among very young patients, for whom the use of a cyclooxygenase-2-specific medication may not be feasible, severely limits options for medical antipyretic treatment. A spirin and other nonsteroidal antiinflammatory drugs (NSAIDs) are a widely used group of medications whose mechanism of action involves inhibition of prostaglandin production through blockade of the cyclooxygenase (COX) enzymes known as COX-1 and COX-2. This blockade also results in the shunting of arachidonic acid metabolism toward the 5-lipoxygenase pathway, resulting in increased production and release of cysteinyl leukotrienes.Acetaminophen, the most ubiquitously used antipyretic medication for children worldwide, is an "old" medication whose mechanism of a...

Hypersensitivity to Paracetamol in Asian Children with Early Onset of Nonsteroidal Anti-Inflammatory Drug Allergy

“…Our previously published protocol [10] is now further modified according to the accumulated experience in small children and the need to tailor challenges to a wide variation in weight and maturity. The published adult protocol for urticaria and angioedema reactions in normal individuals (patients without chronic urticaria) [2] calls for a small initial dose with half-hourly doubling (similar to oral provocation protocols with antibiotics).…”

“…However, it is possible that an early onset of symptomatic hypersensitivity is also a hallmark of increased sensitivity, making paracetamol, with its diminished COX inhibitor capacity but wider exposure, a major eliciting medication for these children. As a group, Asian children, especially atopic children, seem to be at increased risk for hypersensitivity reactions to COX inhibitors [10, 18], with early presenters most likely representing the more severe spectrum of disease.…”

“…Oral provocation tests were performed according to our previously published protocol [10]. In short, all tests were performed in the outpatient clinic of the KKCH.…”

“…The most common clinical presentation of NSAID hypersensitivity in children is facial angioedema (i.e. swelling without itch) [10, 11]. The reported incidence of facial angioedema and NSAID hypersensitivity in a general population of atopic children is about 4.1% on average [12], though it is only 2% below the age of 5 years and rising with age.…”

Ibuprofen: pharmacology, efficacy and safety

“…Asthma and hypersensitivity reactions have long been a cause for concern in children and the cross-reactions of ibuprofen with aspirin-sensitive asthma have been highlighted by several authors (Body and Potier 2004;Kidon et al 2005;Mascia et al 2005;Debley et al 2005;Kanabar 2007;Ponvert and Scheinmann 2007). Two large scale studies in febrile asthmatic children (McIntyre and Hull 1996;Lesko et al 2002) found that ibuprofen far from being associated with increased risk of asthma compared with paracetamol actually showed a slightly reduced risk.…”