Mona Iancovici Kidon

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 Childrens 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.

Increased Mean Platelet Volume and C-Reactive Protein Levels in Patients With Chronic Urticaria With a Positive Autologous Serum Skin Test

Introduction:Activation of the coagulation cascade resulting in thrombin production is a prominent feature of exacerbations in chronic spontaneous urticaria (CU). Autologous serum skin test (ASST) causes wheal-and-flare reactions in 30% to 50% of CU cases. Objective:The aim of this study was to evaluate the clinical and laboratory data in patients with CU with positive and negative ASST. To understand the role of platelets in CU, we investigated the relation between CU clinical severity, platelet count and their mean platelet volume (MPV). Methods:Clinical and laboratory data were prospectively collected from 373 patients with CU who attended our Allergy and Clinical immunology Clinic during the period 2003 to 2007. The laboratory data were compared with 46 healthy subjects. Results:There were no significant differences in platelet counts between the groups, nevertheless the platelets in ASST-positive CU patients were characterized by a higher MPV (9.12 ± 1.25 fl), than that in ASST-negative patients (7.95 ± 1.08 fl; P = 0.039) and control group (7.72 ± 1.04 fl; P = 0.007). There was a significant positive correlation between CU severity score and MPV in ASST-positive patients (r = 0.44; P < 0.001) but not in ASST-negative patients. Higher levels of C-reactive protein (5.31 ± 2.74 mg/L) were measured in the ASST-positive CU group compared with the ASST-negative CU group (2.53 ± 1.27; P = 0.029) and the control group (2.34 ± 1.38; P = 0.003). Conclusion:CU with positive ASST is characterized with higher clinical severity, increased MPV and C-reactive protein.

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 Childrens hospital, from July 2001 to June 2002. A total of 202 patients were included, 161 (80%) males, 167 (83%) Chinese, age mean 7.6u2003yr (range 2–14u2003yr). 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.

Severe Anaphylactic Reaction to Ibuprofen in a Child With Recurrent Urticaria

An acute anaphylactic reaction after a conventional antipyretic dose of ibuprofen was diagnosed in a child with allergic rhinitis, recurrent idiopathic urticaria, and nonimmunologic cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs and acetaminophen. The patient reported several previous, mild (isolated cutaneous) hypersensitivity reactions after exposure to acetaminophen or ibuprofen. There was no evidence of an underlying inflammatory disease except as described above. Patients with chronic or recurrent idiopathic urticaria and those with atopic disease represent groups at increased risk of nonsteroidal antiinflammatory drug hypersensitivity. Mild hypersensitivity reactions to acetaminophen and/or ibuprofen may precede subsequent, more-severe adverse reactions. Risks and benefits of continued use of nonsteroidal antiinflammatory drugs in these children should be carefully considered.

Pulmonary function correlates with arterial stiffness in asthmatic patients

BACKGROUNDnAt the population level, asthma has been associated with chronic systemic inflammation as well as adverse cardiovascular outcomes.nnnOBJECTIVESnThe aim of this study was to investigate peripheral vascular hemodynamic variables of arterial stiffness (AS) and their relationship to pulmonary function tests in asthmatic patients.nnnMETHODSnYoung asthmatic patients from the tertiary center for pulmonary diseases at the Barzilai Medical Center underwent pulmonary function evaluation and non-invasive radial artery hemodynamic profiling, pre- and post-exercise. Results were compared to age matched, non-asthmatic controls.nnnRESULTSn23 young asthmatics and 41 controls, completed all evaluation points. Pulmonary flow parameters were significantly reduced in the asthma group at all points. There were no differences between groups in BMI, blood pressure, pulse rate or measurements of AS at baseline or after bronchodilation. The % predicted forced expiratory volume in the first second at baseline (FEV1%) in asthmatics was positively correlated with the small arteries elasticity index (SAEI) and negatively correlated with the systemic vascular resistance (SVR) in these patients. These correlations were not observed in non-asthmatic controls. In multifactorial regression FEV1 remained the major factor associated with measurements of AS in asthmatic patients, while gender was the only significant factor in non-asthmatic controls.nnnCONCLUSIONSnSignificant correlations between measurements of AS and FEV1 in young asthmatics, suggest the presence of a common systemic, most likely inflammatory pathway involving both the cardiovascular and respiratory systems.

The second generation and asthma: Prevalence of asthma among Israeli born children of Ethiopian origin

BACKGROUNDnImmigrant populations moving from undeveloped countries with low asthma prevalence have shown increased asthma prevalence in their new Westernized environment. We compared the prevalence of asthma among Israeli born children of Ethiopian origin to that in non-Ethiopian children.nnnMETHODSnCross sectional study. Data was retrieved for children aged 6-18 years in four clinics with a large proportion of patients of Ethiopian origin. For each Israeli born child from Ethiopian origin we matched an Israeli born child of any other origin of the same age and gender, receiving primary care from the same physician at the same clinic. Asthma was defined as any visit to a primary care physician, emergency room or hospitalization related to asthma symptoms or subsequent purchasing of any asthma medication during 2008.nnnRESULTSn1217 children of Ethiopian origin and 1217 matched controls were studied. More Ethiopian children came from families with a low socioeconomic status (23.9% vs. 17%, pxa0<xa00.001), and with significantly lower parental smoking (5.1% vs. 40.1%, pxa0<xa00.001). The prevalence of asthma was 92/1217 (7.5%) among children of Ethiopian origin, compared to 122/1217 (10.0%) among the control group (ORxa0=xa00.74, 95% CI: 0.56-0.98, pxa0=xa00.032). When adjusted for tobacco exposure, the OR for risk of asthma in the Ethiopian children was 0.80 (95% CI: 0.59-1.09, pxa0=xa00.16).nnnCONCLUSIONnAsthma prevalence in the second generation of Israeli born children of Ethiopian origin does not seem to differ from other children in their community. This observation supports the theory that environmental exposures, rather than genetic factors, dictated the increase in asthma in this immigrant population.

Pilot study of the use of Yin Qiao San in children with conventional antipyretic hypersensitivity

Background Children with a diagnosis of cross-reactive hypersensitivity to both paracetamol and nonsteroidal anti-inflammatory drugs are limited in their choice of antipyretics. Objective The aim of this pilot study is to evaluate the feasibility of using a Chinese proprietary medicine, Yin Qiao San (YQS), for fever relief. Methods A single centre, open label, prospective clinical trial exploring the tolerability and feasibility of using YQS for fever relief in children who are unable to use conventional antipyretic medications. Children between 1-18 years of age with hypersensitivity to multiple antipyretics were recruited. Eligible participants underwent an oral provocation test with YQS. Children who passed the oral provocation test were instructed to take a prescribed dose of YQS when the temperature was >38.0℃ and continued till the fever settled. Time taken for fever resolution and any adverse events were collected. Results A total of 21 children, mean age 10.7 years, had a diagnosis of paracetamol and ibuprofen hypersensitivity. All except one patient successfully tolerated an oral challenge of YQS. Of the 88 doses of YQS taken for fever over 38.0℃, 16 (18%) had documented temperature reduction 2 hours after ingestion and 30 (34%) had documented temperature reduction 4 hours after ingestion. There were 2 reports of urticaria after YQS use which were attributed to flare of recurrent spontaneous urticaria during the illness. None of the patients developed symptoms of circulatory compromise or respiratory distress. Conclusion YQS is generally well tolerated in patients with paracetamol and ibuprofen hypersensitivity.

EAACI/ENDA Position Paper: Diagnosis and management of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) in children and adolescents

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in the pediatric population as antipyretics/analgesics and anti-inflammatory medications. Hypersensitivity (HS) reactions to NSAID in this age group, while similar to adults, have unique diagnostic and management issues. Although slowly accumulating, published data in this age group are still relatively rare and lacking a unifying consensus. This work is a summary of current knowledge and consensus recommendations utilizing both published data and expert opinion from the European Network of Drug Allergy (ENDA) and the Drug Hypersensitivity interest group in the European Academy of Allergy and Clinical Immunology (EAACI). This position paper summarizes diagnostic and management guidelines for children and adolescents with NSAIDs hypersensitivity.

A Structured Gradual Exposure Protocol to Baked and Heated Milk in the Treatment of Milk Allergy

Objective To evaluate the efficacy and safety of a structured gradual exposure protocol (SGEP) with extensively heated and baked milk in promoting allergy resolution in children with cow milk allergy (CMA). Study design In a case control study, children with CMA aged 1‐4 years who were treated with SGEP including extensively heated and baked milk, were compared with children treated with strict avoidance. Data were collected from medical records and from validated telephone questionnaires. Data analysis was performed using a nonparametric Kaplan‐Meier and proportional hazard Cox regression model, after evaluation of the adequacy of the case control matching. Results There were 43 children with milk allergy—26 (62%) males with a mean age at intervention of 21 months (range, 12‐47 months)—who were treated with SGEP and followed to a mean age of 40 months (range, 20‐82 months). The median age at resolution of CMA was compared with a matched group of 67 children treated with strict avoidance at least until 4 years of age or followed until earlier resolution, with a mean age at follow‐up of 71 months (range, 11‐176 months). The median estimated age at CMA resolution in the SGEP group was 36 months (95% CI, 34.5‐49.7) compared with 98 months (95% CI, 82.4‐114.1) in controls (P < .001). At last follow‐up, 86% of treated children were tolerant to unheated milk proteins vs 52% of controls (P = .003). Conclusion A structured protocol with extensively heated and baked milk seems to promote faster resolution of CMA.