Analysis of drug-induced anaphylaxis cases using the Japanese Adverse Drug Event Report (JADER) database - secondary publication.

BACKGROUND: The epidemiology of drug-induced anaphylaxis using the Japanese nationwide database has been not reported, even though drugs are a common trigger of anaphylaxis. The aim of this study was to describe the epidemiological profile of cases of drug-induced anaphylaxis, including fatal cases, using the data from the Japanese Adverse Drug Event Report database (JADER). METHODS: We extracted data regarding drug-related adverse events, between April 2004 and February 2018, published in JADER by the Pharmaceuticals and Medical Devices Agency. We analyzed cases of anaphylaxis occurring between January 2005 and December 2017. The drug classification was based on the Japanese Standard Commodity Classification. RESULTS: There were 16,916 cases of anaphylaxis reported during the study period. Among them, 418 fatalities were registered. The incidence of drug-induced anaphylaxis and fatal cases was 1.03 cases/year per 100,000 population and 0.03 cases/year, respectively. The most frequent causes of anaphylaxis were diagnostic agents, including X-ray contrast media (20.3%), and biological preparations, such as human blood preparations (20.1%). In fatal cases, diagnostic agents (28.7%) and antibiotic preparations (23.9%) were the most commonly associated types of drugs. CONCLUSIONS: The frequency of drug-induced anaphylaxis and fatalities in Japan remained unchanged over the 13-year period analyzed in this study. Diagnostic agents and biological preparations were the most frequent causes of anaphylaxis; however, fatalities were most frequently caused by either diagnostic agents or antibiotic preparations.

[ANALYSIS OF DRUG-INDUCED ANAPHYLAXIS CASES USING THE JAPANESE ADVERSE DRUG EVENT REPORT DATABASE].

BACKGROUND: The epidemiology of drug-induced anaphylaxis (AN) using the Japanese nationwide database has not been reported, even though drugs are a common trigger of AN. OBJECTIVE: This study aimed to describe the epidemiological profile of drug-induced AN, including fatal cases, using the Japanese Adverse Drug Event Report database (JADER). METHODS: We extracted data regarding drug-induced adverse events between April 2004 and February 2018 published in JADER by the Pharmaceuticals and Medical Devices Agency. We analyzed cases of anaphylaxis occurring between January 2005 and December 2017. The drug classification was based on the Japanese Standard Commodity Classification. RESULTS: There were 16916 cases of anaphylaxis reported during the study period. Among them, 418 fatalities were registered. The incidence of drug-induced AN and fatal cases was 1.03 cases/year per 100000 population and 0.03 cases/year, respectively. The most frequent causes of AN were diagnostic agents including X-ray contrast media (20.3%) and biological agents including human blood preparations (20.1%). In fatal cases, diagnostic agents (28.7%) and antibiotics (23.9%) were the most frequent causes. CONCLUSIONS: The frequency of drug-induced AN and fatalities in Japan remained unchanged over the 12-year period analyzed in this study. Diagnostic and biological agents were the most frequent causes of AN. Contrarily, fatalities were most frequently caused by diagnostic and antibiotic agents.

[A SURVEY ON ACCIDENTAL INGESTION OF PACKAGED PROCESSED FOODS, EATING OUT AND OVER-THE-COUNTER SALES BY INDIVIDUALS WITH FOOD ALLERGIES].

OBJECTIVE: To determine the frequency and effects of accidental ingestion of packaged processed foods, eating out, and over-the-counter sales in individuals with food allergies. METHODS: The participants were guardians of children hospitalized for an oral food challenge test during January and February 2016 at the Department of Pediatrics, Sagamihara National Hospital. We conducted a questionnaire survey on food allergies, accidental ingestion via packaged processed foods, eating out, and over-the-counter sales in the past 1 year, and the degree of understanding of the display of allergen-related information. RESULTS: A total of 442 participants were given questionnaires, and 226 provided valid responses. Among these respondents, 31% had experienced accidental ingestion (packaged processed food: 24%, food service: 12%), and approximately one quarter of the subjects with allergic symptoms had repeated accidental ingestion. About 70% of the causes were due to overlooking or misunderstanding of allergen information. Of the participants, 85% were aware that processed foods must display allergen information, and 39% were aware that there was no requirement to label food sold in food service and over-the-counter sales. CONCLUSIONS: Patients with food allergies are familiar with and repeatedly experience accidental ingestion of packaged processed foods, eating out, and over-the-counter sales. In order to prevent accidental ingestion, it is important to thoroughly check allergy labeling and to instruct patients on precautions to take when eating out or over-the-counter sales.

Nationwide questionnaire-based survey of oral immunotherapy in Japan.

BACKGROUND: Clinical trials on oral immunotherapy (OIT) have been increasing for nearly a decade; however, several national guidelines do not recommend OIT as a standardized procedure. The aim of this study was to obtain insights into the current use and practice of OIT in Japan. METHODS: A first questionnaire was mailed to 524 training and teaching facilities of the Japan Pediatric Society. The first survey requested information on the implementation of OIT, whereas the second survey aimed to gather more detailed information on OIT, such as its safety. RESULTS: In total, 360 facilities (69%) responded to the survey; among them, 102 (28%) provided OIT to 7973 patients [1544 received OIT while hospitalized (inpatient OIT), whereas 6429 received OIT without hospitalization (outpatient OIT)]. Approval for OIT was obtained from an ethics committee or institutional review board in 89% and 31% of facilities for inpatient and outpatient OIT, respectively. In inpatient OIT, immediate allergic reactions requiring treatment occurred in 68% of patients while hospitalized, and in another 56%, following discharge. In contrast, 11% of patients developed immediate allergic reactions in outpatient OIT. Adrenaline injections at home were required in 2%. Sixteen patients developed adverse reactions other than immediate allergic reactions, among which eosinophilic gastroenteritis was most common. CONCLUSIONS: OIT is widely provided not only as clinical research but also as general practice in Japan. However, because there is a high risk of developing anaphylaxis at home, OIT should be conducted carefully as in a clinical research setting taking safety into consideration.

Intermittent and episode-driven use of pranlukast to reduce the frequency of wheezing in atopic children: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Leukotriene receptor antagonist (LTRA) therapy reduces asthma exacerbations in children older than 2 years. However, whether early intervention using LTRA in atopic smaller children aged 1 to 2 years who had experienced episodic wheezing can reduce the frequency of wheezing is unknown. METHODS: A randomized, double-blind, placebo-controlled, multi-center trial of episode-driven intermittent use of pranlukast for 12 months, one of the LTRAs, was conducted by enrolling children who had two, but not more than two, episodes of wheezing prior to entry and were allergen-specific IgE-positive (≥class 2). The primary outcome was increased episodes of wheezing more than once a month for 3 months. RESULTS: Seventy-seven children were randomly assigned to receive pranlukast (n = 37) or placebo (n = 40). The primary outcome occurred in 10 of 36 (28%) of the pranlukast group and 14 of 39 (36%) in the placebo group, which was not significantly different (P = 0.45). Even though the study period was extended to a maximum of >5 years, there was no significant difference in the Kaplan-Meier curves in the occurrence of the primary outcome between the two groups. CONCLUSIONS: These results suggest that intermittent and episode-driven use of pranlukast in small children with a prior history of wheezing and atopic sensitization may not reduce the frequency of wheezing later in life. However, the sample size was too small to make a definitive conclusion. TRIAL REGISTRATION: UMIN000000634.

[Physicians' knowledge with regard to the timing of adrenaline administration for anaphylaxis in Japan].

BACKGROUND: Adrenaline administration is a top priority treatment for severe anaphylaxis. A survey with regard to the timing of adrenaline administration for anaphylaxis was conducted among physicians in Japan. METHODS: The survey was conducted using a questionnaire among physicians who had contributed to a nationwide survey for acute food allergy monitoring in 2011. The questionnaire comprised questions asking physicians whether they possessed registrations as an adrenaline self-injector (ASJ), and timing of adrenaline administration for anaphylaxis. Symptoms of anaphylaxis were categorized into shock or respiratory, gastrointestinal, cutaneous, or laryngeal symptoms. RESULTS: A total of 674 replies were obtained from physicians, and 547 physicians were reported to be registered as ASJs. With regard to time, when patients injected themselves with adrenaline, it resulted in laryngeal (78.4%) and circulatory symptoms (64.4%), whereas when physicians administered adrenaline in patients, it resulted in circulatory (74.8%) and laryngeal symptoms (70.0%). CONCLUSION: Japanese physicians did not necessarily understand the timing of adrenaline administration. Therefore, it is important to provide appropriate education to these physicians with regard to anaphylaxis and ASJ.

[Usefulness of skin prick test using bifurcated needle for the diagnosis of food allergy among infantile atopic dermatitis--second report. In the case of cow's milk allergy].

OBJECTIVE: We investigated the usefulness of skin prick test (SPT) using bifurcated needle (BN) for the diagnosis of cow's milk allergy (CMA) in early infancy. SUBJECTS AND METHODS: Among atopic dermatitis infants with suspicion of food allergy who visited Sagamihara National hospital from January 2001 to April in 2005, 168 cases had received both SPT and IgE ImmunoCAP of CM (CM-IgE) at first visit. We analyzed results of SPT and CM-IgE, focused on infants with negative CM-IgE to examine the usefulness of SPT, and checked positive conversion of CM-IgE with aging. RESULTS: Among 124 infants (73.8%) with negative CM-IgE, 34 infants (27.4%) showed positive SPT results. Forty two infants (33.6%) among the 124 cases were diagnosed as CMA by combination of elimination and provocation test, and 21 infants (50.0%) had positive SPT. In the follow up study of 39 negative CM-IgE cases with CMA, 21 CM-IgE (53.8%) turned positive later infantile period (mean CM-IgE: 4.2+/-4.8 Ua/ml at 9.3+/-5.3 months old). CONCLUSIONS: SPT using BN seemed to be more useful than CM-IgE for the diagnosis of CMA in early infancy with AD. But, the sensitivity is lower than in the egg case.

[Usefulness of skin prick test using bifurcated needle for the diagnosis of food allergy in infantile atopic dermatitis--1st report. Case of egg allergy].

OBJECTIVE: We investigated the usefulness of skin prick test (SPT) for the diagnosis of egg white (EW) allergy in infants with atopic dermatitis who showed negative to EW CAPRAST, and followed up the EW-CAPRAST in this study. SUBJECTS AND METHODS: Data of negative SPT using Bifurcated needle (BN) were analyzed from the data of 202 atopic dermatitis infants, who had received SPT from January in 2001 to April in 2005. From the negative SPT value (average and standard deviation) positive SPT value was obtained. Among 202 cases, 89 suspected-egg allergy infants with negative IgE CAPRAST against EW at the time of first visit were recruited to examine the usefulness of SPT. Positive conversion of EW-CAPRAST was checked in 78 cases (65: egg allergy+, 13: egg allergy(-)) who had been followed up in our outpatient clinic. RESULTS: Range of negative SPT control value (mean+2SD) using BF among infants could be set as less than 2 mm for wheal and/or 5 mm for erythema. Among 89 suspected-egg allergy infants with negative EW-CAPRAST, 72 infants (80.9%) were diagnosed as egg allergy by the combination of elimination and provocation test, interestingly 39 infants (54.2%) showed positive SPT results. In the follow up study of 78 negative EW-CAPRAST cases, 47 EW-CAPRAST out of 65 egg-allergy cases turned positive later infantile period (mean EW-CAPRAST: 9.6+/-16.7 Ua/ml at 9.9+/-5.6 months old). EW-CAPRAST of 7 cases in 13 non-egg allergies also turned positive in the follow up, however EW-CAPRAST titer was relatively lower compared to that of egg allergies (1.1+/-1.5 Ua/ml at 13.3+/-2.6 months old). CONCLUSIONS: We experienced fairly number of atopic infants with negative EW-CAPRAST at the first outpatient visit, who were later diagnosed as egg allergy. In about half of these cases, SPT egg-allergy infants, three quarter of EW-CAPRAST turned positive around 10 months old. EW-CAPRAST of atopic infants without egg allergy also turned transiently and slightly positive. In the conclusions, SPT seemed to be more useful than EW-CAPRAST for the diagnosis of egg allergy in early infantile period, however provocation test should be required for the definitive diagnosis in suspected-egg allergy infants without any proof of egg-sensitization.

[Investigation on the usage and prescription of adrenaline self-injector against anaphylaxis].

BACKGROUND: In Japan Adrenaline self injector (ASJ) became available for patients with anaphylaxis including children in 2005. Countermeasure against anaphylaxis in Japan is far behind international standards, and understanding of anaphylaxis and its treatment by doctors is thought to be unsatisfactory level. METHODS AND SUBJECTS: This investigation was carried out using questionnaire towards 1,196 doctors who had contributed nationwide survey of food allergy monitoring in 2005. The investigation was done on January in 2006. The questionnaire consisted of possession of registration as ASJ prescription doctor, prescription experience, indication of ASJ prescription, and timing for patients to use ASJ. RESULTS: Seven hundred and seven replies were obtained out of 1,196 doctors, and 443 doctors (62.7%) were reported to be registered as an ASJ prescription doctors. Among 443 registered doctors, 209 doctors had experienced to prescribe ASJ. Only 88 percent of doctors accepted the cases with repeated anaphylaxis as criteria for absolute prescription of ASJ, and 41.6 percent of doctors accepted cases with history of anaphylaxis as the criteria. Timing by doctors to inject adrenaline was reported to be cases with circulatory symptom (93.7%), airway mucosa symptom (79.4%), and with respiratory symptom (56.6%), DISCUSSION: Japanese doctors seem to have unsatisfactory level of knowledge of anaphylaxis . It is important for Japanese doctors to receive appropriate education on anaphylaxis and ASJ.

[Allergenic activity of non-calcinated egg shell calcium].

BACKGROUND: There is few data to prove the safety of egg shell calcium as allergen. Especially, non-calcinated egg shell calcium is not allowed to use without the description of origin of egg on food labels in Japan. METHOD: We evaluated the possibly contaminated egg allergens in commercial non-calcinated egg shell calcium made from egg by in vitro methodologies (SDS-PAGE, western blotting, inhibition ELISA and sandwich ELISA) and by single-blind oral non-calcinated egg shell calcium challenge on 6 egg hypersensitivity patients. RESULTS: The allergenic activity of non-calcinated egg shell calcium was almost negligible compared to egg white by all in vitro methods. Furthermore, six patients with egg hypersensitivity were unresponsive to oral non-calcinated egg shell calcium challenge test. CONCLUSION: These results indicate that there is little contamination of egg white in non-calcinated egg shell calcium, and that the allergenic activity of non-calcinated egg shell calcium is equivalent to that of calcinated egg shell calcium.