Early presentation with angioedema and urticaria in cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs among young, Asian, atopic children.

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 hospital-based 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 cross-reactive 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.

The Pediatric Rheumatology International Trials Organization criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set.

OBJECTIVE: To validate and promulgate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile systemic lupus erythematosus (SLE). METHODS: In 2001, a preliminary consensus-derived core set of measures for evaluating the response to therapy in juvenile SLE was established. In the present study, the core set was validated through an evidence-based, large-scale data collection process that led to the enrollment of 557 patients from 39 different countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, agreement in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. RESULTS: The following clinical measures were found to be feasible and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician's global assessment of disease activity, 2) global disease activity measure, 3) 24-hour proteinuria, 4) parent's global assessment of the patient's overall well-being, and 5) health-related quality of life assessment. CONCLUSION: The members of PRINTO propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a patient with juvenile SLE has responded adequately to therapy.

Bimodal skin reactivity to histamine in atopic children in Singapore: influence of specific sensitizations.

Histamine skin prick test (SPT) is used as the 'golden standard' for positive control in in vivo immediate type hypersensitivity testing. The skin reactivity to histamine can, however, be modulated by a bevy of extraneous factors. We aimed to define whether histamine skin reactivity in atopic children in Singapore is influenced by age, ethnic origin, gender, environmental exposure or specific sensitization patterns. A retrospective analysis of children, with specific aeroallergen sensitization (as measured by at least one allergen-specific SPT with a wheal size > 3 mm compared with the negative control) from the outpatient speciality clinic of the KK Children's Hospital, during 06/2002-06/2003. A total of 315 patients were included, 235 (75%) were males, 252 (80%) were Chinese, age mean was 7.7 yr (range: 2-15). Patients were referred to the SPT with a diagnosis of one or more of: allergic rhinitis 287 (91%), asthma 112 (36%) or atopic dermatitis 60 (19%). The mean histamine response showed a bimodal distribution, independent of age, ethnic origin, gender or phenotypical expression of allergic disease. Histamine skin reactivity was higher in atopic patients with polysensitization (mean 5.0 mm vs. 2.9 mm in monosensitized patients, p < 0.001), and in patients with mould sensitization (mean 5.1 mm vs. 3.3 mm in patient not sensitized to moulds, p < 0.001). The presence of passive smoking increased the likelihood of a diminished histamine skin response. Histamine skin response data strongly suggested the presence of two heterogeneous subpopulations. Children with polysensitization and mould sensitization were more likely to show a large significant histamine response, whereas children with passive smoke exposure, showed a diminished skin reactivity to histamine.

Aeroallergen sensitization in pediatric allergic rhinitis in Singapore: is air-conditioning a factor in the tropics?

Singapore is a unique blend of a tropical environment with a high standard of hygiene and public health care. The objective was to define the prevalence, clinical characteristics, and environmental risk factors of specific aeroallergen sensitization in pediatric allergic rhinitis patients in this unique environment. The method adopted was a retrospective analysis of allergic rhinitis patients, undergoing aeroallergen skin prick testing (SPT), in the outpatient specialty clinic of the KK Children's hospital, from July 2001 to June 2002. A total of 202 patients were included, 161 (80%) males, 167 (83%) Chinese, age mean 7.6 yr (range 2-14 yr). The most prevalent clinical symptoms were: watery rhinorrhea 61%, blocked nose 61%, sneezing 52%, snoring 17%, and epistaxis 12%. SPT results were positive for house dust mites in 97% of children, pets (20%), molds (19%), pollens (15%), and kapok (10%). Mold sensitization was significantly more prevalent in households without air-conditioning (aircon), 49% vs. 10% with aircon (odds ratio 9.4, 95% CI 3.8-22.9). Polysensitization (sensitization to three or more allergens) was similarly more prevalent in households without aircon, 51% vs. 14% with aircon (odds ratio 6.4, 95% CI 2.8-14.7). It was concluded that indoor aeroallergen sensitization is the major associated factor with clinical allergic rhinitis in children in Singapore. Patients living in households without air-conditioning are at increased risk of mold sensitization and polysensitization.