Outcomes of drug provocation tests in Korean children with suspected drug hypersensitivity reaction

PURPOSE: Drug provocation tests (DPT) are the gold standard for confirming the diagnosis of drug hypersensitivity reactions (DHRs). However, there are little studies of DPT in children. The purpose of this study was to evaluate DPT results and safety as diagnostic methods of DHR in Korean children. METHODS: We reviewed the medical records of 39 children under 18 years of age with a suspected DHR and performed DPT between January 2010 and May 2016 at Asan Medical Center. RESULTS: Total 110 DPT were performed in 39 children (20 boys and 19 girls) with a history of DHR. Clinical presentation of DHR included skin rash (n=7), pruritus (n=3), urticaria (n=18), angioedema (n=19), dyspnea (n=5), hoarseness (n=1), hypothermia (n=1), and anaphylaxis (n=5). The median age at the time of DPT was 9 years. Positive DPT were observed in 21 of 39 children (53.8%) and 28 of 110 cases (25.5%). Drugs causing positive reactions were acetaminophen in 50% (9 of 18), nonsteroidal anti-inflammatory drugs in 29.2% (14 of 48), cephalosporin in 9.1% (1 of 11), trimethoprim/sulfamethoxazole in 50% (1 of 2), local anesthetics in 10% (1 of 10), and others (levodropropizine and idursulfase) in 15.4% (2 of 13). There was no statistical difference between children who had positive and negative results in sex, age, personal and parental history of allergic disease, eosinophil count, or total IgE level. Children with positive DPT did not develop anaphylaxis during the DPT procedure. CONCLUSION: Drug provocation test is safe, and it can be considered in children with suspected DHRs.

Pediatric adverse drug reactions collected by an electronic reporting system in a single tertiary university hospital

PURPOSE: The incidence of adverse drug reactions (ADRs) is increasing. However, studies on the prevalence of ADRs in children are rare. The aim of this study was to investigate the causative drugs and clinical features of ADRs for children in a tertiary university hospital of Korea. METHODS: We retrospectively collected ADRs by a computerized self-reporting system in Asan Medical Center. ADRs of children under the age 18 were collected from January 2005 to August 2015, and we analyzed only ADRs containing current symptoms among total ADR data. RESULTS: A total of 1,408 ADR cases were reported, There were 764 male (54.3%) and 644 female patients (45.7%), and the mean age was 11.5±5.8 years (range, 0–18 years). Antibiotics (n=479, 34.0%) were the most common causative drugs, followed by tramadol (n=173, 12.3%), nonsteroidal anti-inflammatory agents (NSAIDs) and acetylsalicylic acid (n=103, 7.3%), narcotics (n=91, 6.5%), antineoplastics (n=87, 6.2%), and sedatives (n=82, 5.8%). The most common clinical features were skin manifestations (n=500, 34.4%). Gastrointestinal symptoms (n=435, 29.9%) were the second most common clinical features, followed by neuropsychiatric symptoms (n=155, 10.7%) and respiratory symptoms (n=123, 8.5%). Among antibiotics, glycopeptides (n=110, 23.0%), third-generation cephalosporins (n=83, 17.3%), and penicillin/β-lactamase inhibitors (n=60, 12.7%) were the most frequently reported causative drugs. CONCLUSION: Antibiotics were the most reported common causative drugs of ADRs in children, followed by tramadol, NSAID, and narcortics. Compared with adults, the prevalence of contrast medium-induced ADR was lower in children with a higher prevalence of sedative-associated ADR. Greater attention to possible ADRs in children is needed among medical personnel.

The Association of Lung Function, Bronchial Hyperresponsiveness, and Exhaled Nitric Oxide Differs Between Atopic and Non-atopic Asthma in Children

PURPOSE: Although many previous studies have attempted to identify differences between atopic asthma (AA) and non-atopic asthma (NAA), they have mainly focused on the difference of each variable of lung function and airway inflammation. The aim of this study was to evaluate relationships between lung function, bronchial hyperresponsiveness (BHR), and the exhaled nitric oxide (eNO) levels in children with AA and NAA. METHODS: One hundred and thirty six asthmatic children aged 5-15 years and 40 normal controls were recruited. Asthma cases were classified as AA (n=100) or NAA (n=36) from skin prick test results. Lung function, BHR to methacholine and adenosine-5'-monophosphate (AMP), eNO, blood eosinophils, and serum total IgE were measured. RESULTS: The AA and NAA cases shared common features including a reduced small airway function and increased BHR to methacholine. However, children with AA showed higher BHR to AMP and eNO levels than those with NAA. When the relationships among these variables in the AA and NAA cases were evaluated, the AA group showed significant relationships between lung function, BHR to AMP or methacholine and eNO levels. However, the children in the NAA group showed an association between small airway function and BHR to methacholine only. CONCLUSIONS: These findings suggest that the pathogenesis of NAA may differ from that of AA during childhood in terms of the relationship between lung function, airway inflammation and BHR.

High degree of supervision improves adherence to inhaled corticosteroids in children with asthma / 소아과

PURPOSE: Adherence to treatment with inhaled corticosteroids (ICS) is a critical determinant of asthma control. The objective of this study was to assess factors that determine adherence to ICS therapy in children with asthma. METHODS: Fifty-eight children with asthma, aged 5 to 16 years, used ICS with or without a spacer for 3 months. Adherence rates as measured from questionnaires and canisters, asthma symptom scores, and inhalation technique scores were assessed every 30 days. The degree of supervision by caregivers was assessed at day 30. RESULTS: Adherence rates measured using canisters were lower at day 60 than at day 30 (P=0.044) and did not change thereafter (74.4%+/-17.4% at day 30, 66.5%+/-18.4% at day 60, and 67.4%+/-22.2% at day 90). Adherence rates at days 60 and 90 and during the total study period were significantly different when measured by using questionnaires versus canisters (P<0.001, P=0.022, and P=0.001, respectively). In the comparison of adherence rates repeatedly measured at days 30, 60, and 90 and adherence rates during the total study period among the 3 groups, adherence rates in the high-degree supervision group were significantly higher than those in the low-degree supervision group (82.0+/-16.0 vs. 66.1+/-14.5, 75.4+/-14.4 vs. 56.2+/-18.4, 75.0+/-18.3 vs. 55.0+/-19.7 [P=0.027]; 77.9+/-12.2 vs. 59.1+/-11.4 [P=0.021]) after adjustment for sex and age. CONCLUSION: The level of caregiver supervision is an important factor affecting adherence to ICS therapy in children with asthma. Therefore, a high degree of supervision may be required to increase adherence to ICS therapy in children with asthma.

Delayed urticaria caused by lidocaine in a child

Lidocaine is a commonly used local anesthetic for dental treatment. Urticaria caused by lidocaine has seldom been reported. Generally, urticaria immediately develops after exposure to a causative agent and is considered a manifestation of IgE-mediated hypersensitivity. However, delayed urticaria caused by local anesthetics was reported to be related to cell mediated hypersenstivity. A 3-year old girl visited our allergy clinic due to delayed urticaria after local administration of lidocaine. Both skin prick and intradermal tests with lidocaine revealed negative reactions. However, the provocation test with subcutaneous injection of lidocaine showed urticaria 7 hours after test. In order to identify alternative local anesthetic for the subsequent dental procedure, we performed skin prick, intradermal and provocation tests with procaine, a local anesthetic of the other class, all of which showed negative results. Therefore, we recommended procaine as an alternative local anesthetic, and the patient was successfully treated with procaine. To the best of our knowledge, this is the first case of delayed urticaria caused by lidocaine in Korea.

Changes of aeroallergen sensitization in children with asthma or allergic rhinitis from a tertiary referral hospital in Seoul over 10 years

PURPOSE: Allergic diseases have been increased in Korea. The aim of this study was to investigate the changes of sensitization rate to inhalant allergens over 10 years in children with allergic diseases from a tertiary referral hospital. METHODS: Skin prick tests were done in total 2,225 children in 2000, 2005, and 2010. Changes of skin reactivity to 12 major inhalant allergens, including Tree pollen mixture I (Alder, Elm, Hazel, Poplar, Willow), Tree pollen mixture II (Beech, Birch, Oak, Plane tree), Dermatophagoides pteronyssinus, Dermatophagoides farina, Alternaria, cat dander, and dog dander were investigated. RESULTS: The sensitization rates to Tree pollen mixture I and II were increased as 5.0%, 6.8% in 2000, 8.5%, 9.8% in 2005, and 14.8%, 17.3% in 2010, respectively (trend P<0.001, P<0.001, respectively). And the sensitization rates to D. pteronyssinus cat dander and dog dander were changed as 55%, 4.8%, 4.8% in 2000, 62.2%, 11.9%, 28% in 2005, and 63.1%, 12.7%, 16.7% in 2010, respectively. The distribution of sensitized pollens was oak (12.8%), beech (12.4%), pine (10.3%), birch (10%), hazel (9.6%), alder (8%), elder (6.9%), elm (5.4%) in the study of 2010. When allergen/histamine ratio was compared, rates of strong sensitization over 4+ to tree pollen were increased. CONCLUSION: The sensitization rates to inhalant allergens were increased in children with asthma or allergic rhinitis from a tertiary referral hospital in Seoul over last 10 years. Especially, an increase in the degree of skin reactivity was observed in cat dander, dog dander, and tree pollens. The studies to investigate the etiology of this increase and prevention will be needed.

Four Cases of Drug Allergy Caused by Non-Steroidal Anti-Inflammatory Drugs in Children / 소아알레르기및호흡기학회지

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), which reduce the production of prostaglandin by inhibiting cyclooxygenase (COX), are widely used in children as antipyretic, analgesic, or anti-inflammatory drugs. They are known to be a major cause of pediatric drug allergies, which are diagnosed by a drug provocation test. The mechanism comprises an immunoglobulin E- or T cell-mediated immune reaction or pseudoallergy caused by the inhibition of COX-1. The diagnosis of NSAIDs drug allergy requires a differential, because there is a high cross-reactivity between NSAIDs. In this study, oral provocation tests with ibuprofen, acetaminophen, diclofenac and celecoxib were carried out, and various types of NSAIDs and acetaminophen allergies were observed. Safe drugs were recommended for each patient according to the test results. We report four cases of NSAIDs and acetaminophen allergy and include the results of oral provocation tests.