Changes in Australian food anaphylaxis admission rates following introduction of updated allergy prevention guidelines.

BACKGROUND: Food anaphylaxis admission rates have increased steadily in recent decades. Global food allergy prevention guidelines recommending early introduction of allergenic foods were introduced in 2015-2016. Australian guidelines to not delay the introduction of allergenic foods were introduced in 2007-2008. OBJECTIVE: Our aim was to examine whether introduction of Australian guidelines (2007-2008) and global allergy prevention guidelines (2015-2016) were associated with reductions in food anaphylaxis admission rates. METHODS: We compared food anaphylaxis admission rates across 3 periods: 1998-1999 to 2006-2007, 2007-2008 to 2014-2015, and 2015-2016 to 2018-2019. RESULTS: Annual food anaphylaxis admission rates increased 9-fold between 1998-1999 and 2018-2019, from 2.0 per 105 population to 18.2 per 105 population; the highest absolute rates were in those younger than 1 year. When year-on-year rates of change were examined across the 3 time periods, the annual rate of increase slowed after 2007-2008 in those aged 1 to 4 years (17.6%, 6.2%, and 3.9% per year, respectively) and those aged 5 to 9 years (22%, 13.9%, and -2.4%, respectively), and after 2015-2016, in those aged 10 to 14 years (17.5%, 18.0%, and 10.8%, respectively). By contrast, the year-on-year rate of increase accelerated in those younger than 1 year (5.2%, 8.0%, and 18.0%, respectively) and in all age groups older than 15 years. CONCLUSIONS: Although food anaphylaxis continues to increase overall, there is preliminary evidence indicating a slowing in the year-on-year rate of increase among those aged 1 to 4, 5 to 9, and 10 to 14 years, coinciding with introduction of updated infant feeding and allergy prevention guidelines in 2007-2008 and 2015-2016. Changes to the guidelines may have contributed to an attenuated rate of increase in food anaphylaxis in these age groups, as well as to increased rates in those younger than 1 year.

Increasing anaphylaxis events in Western Australia identified using four linked administrative datasets.

BACKGROUND: Anaphylaxis events are increasing worldwide, based on studies of single administrative datasets including hospital admissions, emergency room presentations, and prescription and medical claims data. Linking multiple administrative datasets may provide better epidemiological estimates, by capturing a greater number of anaphylaxis events occurring at the individual level. In this linked data study in Western Australia, we combined 4 population-based datasets to identify anaphylaxis events, factors influencing occurrence, and change in event rates from 2002 to 2013. METHODS: Four linked administrative datasets from the Western Australian Data Linkage System were used, representing ambulance attendances, emergency department presentations, hospital inpatient admissions and death registrations. An anaphylaxis cohort was identified using ICD-9-CM, ICD-10-AM and additional anaphylaxis diagnosis codes, with event rates calculated. We explored the impact of age, gender, cause, Indigenous status and socioeconomic index on event rates. Standard Poisson regression models were used to examine the significance of the change in anaphylaxis event rates over time. RESULTS: A total 12,637 individuals (mean age 31.8 years, 49.6% female) experienced 15,462 anaphylaxis events between 2002 and 2013 (97.5% in non-Indigenous patients and 59.5% residing in the area of greatest socioeconomic advantage). Anaphylaxis event rates increased from 15.4 to 82.5/105 population between 2002 and 2013. The greatest increase in anaphylaxis events was seen in those coded as unspecified anaphylaxis (all ages, males and females combined, p < 0.001), with the highest rates of unspecified anaphylaxis in males 0-4 years (171.9/105 population in 2013), and females 15-19 years (104.0/105 in 2013). The average annual percent increase (95% CI) for food-related anaphylaxis was 9.2% (6.6-12.0); for medication-related anaphylaxis was 5.8% (4.5-7.1); and for unspecified anaphylaxis was 10.4% (9.8-11.0); all p < 0.001. There was a significant increase in ambulance attendance, emergency presentations and inpatient admissions for anaphylaxis between 2002 and 2013, with emergency presentations (56.0/105 population), inpatient admissions (43.2/105), and ambulance attendance (21.6/105) highest in 2013. Only 25 anaphylaxis-related deaths were recorded in the mortality register with no significant change in rates over time. CONCLUSION: Using multiple linked administrative datasets, we identified significantly higher rates of total anaphylaxis than previously reported, with more than 5-fold increases in anaphylaxis events between 2002 and 2013. While the combination of 4 population-level datasets provides a more comprehensive capture of cases, even at the individual dataset level, admission rates for anaphylaxis in Western Australia are substantially higher than those previously reported for similar time periods, both in Australia and worldwide.

Multicenter Australian Study to Determine Criteria for Low- and High-Risk Penicillin Testing in Outpatients.

BACKGROUND: Recent single-center studies promote oral penicillin challenges, without skin testing, in patients with low risk/likelihood of true allergy. However, how best to define a low-risk penicillin allergy history is uncertain. OBJECTIVE: To statistically determine an optimal low-risk definition, to select patients for safe outpatient penicillin challenges, without skin testing. METHODS: In a multicenter Australian study (February 2016 to May 2018), testing strategy (skin test and/or oral penicillin challenge) and outcomes were retrospectively collected for all penicillin-allergic patients. Statistical modeling was performed with 8 low-risk definitions, to determine an optimal low-risk definition. RESULTS: A total of 447 subjects (mean age, 45.3 years; 63.8% females) were analyzed. A history of benign, immediate, or delayed rash, more than 1 year before review, was the optimal low-risk definition. A total of 244 of 447 (54.6%) patients met this definition, of which 97.1% tolerated a 1- or 2-dose penicillin challenge, with no anaphylaxis in those who reacted. Of 203 patients designated higher risk, 54 (26.6%) had their allergy confirmed by skin test (n = 45) or challenge (n = 9). CONCLUSIONS: History of penicillin-associated rash (without angioedema, mucosal ulceration, or systemic involvement), more than 1 year ago, is sufficient to select a patient for a direct oral penicillin challenge. This large multicenter study demonstrates that this approach appears safe, and risk is comparable to that in other procedures being performed in primary care in Australia. The higher risk patients are more likely to benefit from skin testing. This simple risk-based delabeling strategy could potentially be used by nonallergists, leading to more efficient penicillin allergy delabeling service provision.

Allergic gastroenteritis hospital admission time trends in Australia and New Zealand.

AIM: Recent epidemiological studies indicate increases in hospital food allergy-related anaphylaxis admission rates in Australian and New Zealand. The aim of the study was to examine whether non-IgE-mediated food allergy might have increased in parallel. METHODS: We analysed childhood hospital admissions rates by ICD 10 codes for allergic gastroenteritis (AG) and infective gastroenteritis in Australia and New Zealand between June 1998 and July 2014. RESULTS: In Australia, most AG-related admissions (73%) occurred in those aged <1 year and increased by 7.3%/year (95% confidence interval (CI) 5.5-9.3, P < 0.0001) from 6.8 to 26.5/105 population. Similar trends were observed for New Zealand; 81% of admissions occurred in those aged <1 year and increased by 9.4%/year (95% CI 5.5-9.3, P < 0.0001) from 7.2 to 30.7/105 population. By contrast there were no significant changes in AG-related admission rates in the older patients and infective gastroenteritis admissions fell in both countries in those aged <1 year; Australia by 4.4%/year (95% CI 4.3-4.6, P < 0.0001) and in New Zealand by 5.8%/year (95% CI 5.4-6.2, P < 0.0001). CONCLUSION: We observed a fourfold increase in AG-related admission rates in two countries with known high rates of IgE-mediated food allergy/anaphylaxis. If confirmed by other studies, it will be of interest to determine if factors thought to contribute to the increase in IgE-mediated food allergy might also play a role in non-IgE-mediated gastroenterological food allergy syndromes.

Food allergy: is prevalence increasing?

It is generally accepted that the prevalence of food allergy has been increasing in recent decades, particularly in westernised countries, yet high-quality evidence that is based on challenge confirmed diagnosis of food allergy to support this assumption is lacking because of the high cost and potential risks associated with conducting food challenges in large populations. Accepting this caveat, the use of surrogate markers for diagnosis of food allergy (such as nationwide data on hospital admissions for food anaphylaxis or clinical history in combination with allergen-specific IgE (sIgE) measurement in population-based cohorts) has provided consistent evidence for increasing prevalence of food allergy at least in western countries, such as the UK, United States and Australia. Recent reports that children of East Asian or African ethnicity who are raised in a western environment (Australia and United States respectively) have an increased risk of developing food allergy compared with resident Caucasian children suggest that food allergy might also increase across Asian and African countries as their economies grow and populations adopt a more westernised lifestyle. Given that many cases of food allergy persist, mathematical principles would predict a continued increase in food allergy prevalence in the short to medium term until such time as an effective treatment is identified to allow the rate of disease resolution to be equal to or greater than the rate of new cases.

ASCIA guidelines for prevention of anaphylaxis in schools, pre-schools and childcare: 2015 update.

The aim of these guidelines is to assist staff in school and childcare settings to plan and implement appropriate risk minimisation strategies, taking into consideration the needs of the allergic child, the likely effectiveness of measures and the practicality of implementation. Although these guidelines include risk minimisation strategies for allergic reactions to insect stings or bites, latex and medication, the major focus relates to food allergy. This is due to the higher relative prevalence of food allergy in childhood (compared with other allergic triggers) and the higher likelihood of accidental exposure in these settings. Care of the allergic child in the school, pre-school or childcare settings requires accurate information obtained from parents and carers, staff training in the recognition and management of acute allergic reactions, planning for unexpected reactions (including in those not previously identified as being at risk), age appropriate education of children with severe allergies and their peers, and implementation of practical strategies to reduce the risk of accidental exposure to known allergic triggers. Strategy development also needs to take into account local or regional established legislative or procedural guidelines and the possibility that the first episode of anaphylaxis may occur outside the home. Food bans are not recommended as the primary risk minimisation strategy due to difficulties in implementation and lack of proven effectiveness.

Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012.

BACKGROUND: Studies from the United Kingdom, the United States, and Australia have reported increased childhood food allergy and anaphylaxis prevalence in the 15 years after 1990. OBJECTIVE: We sought to examine whether childhood food allergy/anaphylaxis prevalence has increased further since 2004-2005. METHODS: We examined hospital anaphylaxis admission rates between 2005-2006 and 2011-2012 and compared findings with those from 1998-1999 to 2004-2005. RESULTS: Overall population food-related anaphylaxis admission rates (per 10(5) population per year) increased from 5.6 in 2005-2006 to 8.2 in 2011-2012 (a 1.5-fold increase over 7 years). The highest rates occurred in children aged 0 to 4 years (21.7 in 2005-2006 and 30.3 in 2011-2012, a 1.4-fold increase), but the greatest proportionate increase occurred in those aged 5 to 14 years (5.8-12.1/10(5) population/y, respectively, a 2.1-fold increase) compared with those aged 15 to 29 years and 30 years or older (a 1.5- and 1.3-fold increase, respectively). Not only did absolute food-related anaphylaxis admissions increase, but the modeled year-on-year rate of increase in overall food-related anaphylaxis admissions also increased over time from an additional 0.35 per 10(5) population/y in 1998-1999 (all ages) to 0.49 in 2004-2005 and 0.63 in 2011-2012 (P < .001). CONCLUSIONS: Food-related anaphylaxis has increased further in all age groups since 2004-2005. Although the major burden falls on those aged 0 to 4 years, there is preliminary evidence for a recent acceleration in incidence rates in those aged 5 to 14 years. This contrasts with the previous decade in which the greatest proportionate increase was in those aged 0 to 4 years. These findings suggest a possible increasing burden of disease among adolescents and adults who carry the highest risk for fatal anaphylaxis.

Ant venom immunotherapy in Australia: the unmet need.

Jack jumper ant (JJA) venom allergy is an important cause of anaphylaxis in south-eastern Australia. The efficacy and real-world effectiveness of JJA venom immunotherapy (VIT) to prevent anaphylaxis in allergic patients are now well established, with an evidence base that is at least equivalent to that supporting VIT for allergy to other insect species. The tolerability and safety of JJA VIT are comparable with those of honeybee VIT.

ASCIA guidelines for prevention of anaphylaxis in schools, pre-schools and childcare: 2012 update.

Appropriate management and prevention of anaphylaxis in the school, pre-school and childcare settings requires advanced planning and communication. The Australasian Society of Clinical Immunology and Allergy has developed Guidelines for Prevention of Anaphylaxis in Schools, Pre-schools and Childcare to assist school, pre-school and childcare staff in appropriate implementation of risk-minimisation strategies. Risk-minimisation strategies recommended take into consideration the needs of the allergic child; effectiveness of measures; stresses on parents and staff, the allergic child and their peers; and the implications of the recommended risk-minimisation strategies. These Guidelines address risk-minimisation strategies for food, insect and medication allergies; however, the majority of strategies relate to food allergy due to the higher risk of exposure in these settings. Training in recognition of allergic symptoms (including anaphylaxis), appropriate response and treatment, as well as how to prevent exposure to known allergens are essential for effective anaphylaxis management in the school, pre-school and childcare settings.

Neonatal vitamin D status and childhood peanut allergy: a pilot study.

BACKGROUND: Although a number of factors have been proposed to explain the increase in food allergy during the last decade, the possibility that vitamin D status may play a pathogenic role has received recent attention. OBJECTIVE: To determine whether lower levels of neonatal 25-hydroxyvitamin D (25[OH]D) would be observed in children with peanut allergy compared with in population controls. METHODS: The concentration of 25(OH)D was measured from neonatal dried blood samples by liquid chromatography tandem mass spectrometry. Levels were compared between children with IgE-mediated peanut allergy younger than 72 months assessed during 2008-2011 in a specialist referral clinic in the Australian Capital Territory and population births matched by sex, birth date, and birth location. Odds ratios were calculated for the matched pairs across quintiles of 25(OH)D. RESULTS: Neonatal 25(OH)D levels ranged from 8 to 180 nmol/L (median, 66 nmol/L; interquartile range, 46-93 nmol/L); only 4 children (3%) had levels less than 25 nmol/L, and 24 (20.9%) had levels greater than 100 nmol/L. No significant association was found between socioeconomic or clinical factors and 25(OH)D levels. Compared with the reference group (50-74.9 nmol/L), levels of 75 to 99.9 nmol/L were associated with lower risk of peanut allergy (P = .02). No further reduction was found at levels of 100 nmol/L or higher, and the risk of peanut allergy at levels less than 50 nmol/L was not significantly different from the reference group. CONCLUSION: The relationship between neonatal 25(OH)D level and childhood peanut allergy was nonlinear, with slightly higher levels (75-99.9 nmol/L) associated with lower risk than those in the reference group (50-74.9 nmol/L). Vitamin D status may be one of many potential factors contributing to childhood peanut allergy pathogenesis.

Relationship between red meat allergy and sensitization to gelatin and galactose-α-1,3-galactose.

BACKGROUND: We have observed patients clinically allergic to red meat and meat-derived gelatin. OBJECTIVE: We describe a prospective evaluation of the clinical significance of gelatin sensitization, the predictive value of a positive test result, and an examination of the relationship between allergic reactions to red meat and sensitization to gelatin and galactose-α-1,3-galactose (α-Gal). METHODS: Adult patients evaluated in the 1997-2011 period for suspected allergy/anaphylaxis to medication, insect venom, or food were skin tested with gelatin colloid. In vitro (ImmunoCAP) testing was undertaken where possible. RESULTS: Positive gelatin test results were observed in 40 of 1335 subjects: 30 of 40 patients with red meat allergy (12 also clinically allergic to gelatin), 2 of 2 patients with gelatin colloid-induced anaphylaxis, 4 of 172 patients with idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02-0.4 g), and 4 of 368 patients with drug allergy. Test results were negative in all patients with venom allergy (n = 241), nonmeat food allergy (n = 222), and miscellaneous disorders (n = 290). ImmunoCAP results were positive to α-Gal in 20 of 24 patients with meat allergy and in 20 of 22 patients with positive gelatin skin test results. The results of gelatin skin testing and anti-α-Gal IgE measurements were strongly correlated (r = 0.46, P < .01). α-Gal was detected in bovine gelatin colloids at concentrations of approximately 0.44 to 0.52 µg/g gelatin by means of inhibition RIA. CONCLUSION: Most patients allergic to red meat were sensitized to gelatin, and a subset was clinically allergic to both. The detection of α-Gal in gelatin and correlation between the results of α-Gal and gelatin testing raise the possibility that α-Gal IgE might be the target of reactivity to gelatin. The pathogenic relationship between tick bites and sensitization to red meat, α-Gal, and gelatin (with or without clinical reactivity) remains uncertain.

Latitude, sunlight, vitamin D, and childhood food allergy/anaphylaxis.

Vitamin D is widely known for its role in bone metabolism, but this sterol hormone also has important immunomodulatory properties. Vitamin D is produced by the conversion of D3 in the skin following UVB exposure, or after ingestion of D2 or D3. At the extremes of latitude, there is insufficient UVB intensity in the autumn and winter months for adequate synthesis of vitamin D to occur. Growing evidence implicates vitamin D deficiency in early life in the pathogenesis of nonskeletal disorders (e. g., type 1 diabetes and multiple sclerosis) and, more recently, atopic disorders. Several studies have reported higher rates of food allergy/anaphylaxis or proxy measures at higher absolute latitudes. Although causality remains to be determined, these studies suggest a possible role for sunlight and/or vitamin D in the pathogenesis of food allergy/anaphylaxis.

Causes of ant sting anaphylaxis in Australia: the Australian Ant Venom Allergy Study.

OBJECTIVE: To determine the Australian native ant species associated with ant sting anaphylaxis, geographical distribution of allergic reactions, and feasibility of diagnostic venom-specific IgE (sIgE) testing. DESIGN, SETTING AND PARTICIPANTS: Descriptive clinical, entomological and immunological study of Australians with a history of ant sting anaphylaxis, recruited in 2006-2007 through media exposure and referrals from allergy practices and emergency physicians nationwide. We interviewed participants, collected entomological specimens, prepared reference venom extracts, and conducted serum sIgE testing against ant venom panels relevant to the species found in each geographical region. MAIN OUTCOME MEASURES: Reaction causation attributed using a combination of ant identification and sIgE testing. RESULTS: 376 participants reported 735 systemic reactions. Of 299 participants for whom a cause was determined, 265 (89%; 95% CI, 84%-92%) had reacted clinically to Myrmecia species and 34 (11%; 95% CI, 8%-16%) to green-head ant (Rhytidoponera metallica). Of those with reactions to Myrmecia species, 176 reacted to jack jumper ant (Myrmecia pilosula species complex), 18 to other jumper ants (15 to Myrmecia nigrocincta, three to Myrmecia ludlowi) and 56 to a variety of bulldog ants, with some participants reacting to more than one type of bulldog ant. Variable serological cross-reactivity between bulldog ant species was observed, and sera from patients with bulldog ant allergy were all positive to one or more venoms extracted from Myrmecia forficata, Myrmecia pyriformis and Myrmecia nigriceps. CONCLUSION: Four main groups of Australian ants cause anaphylaxis. Serum sIgE testing enhances the accuracy of diagnosis and is a prerequisite for administering species-specific venom immunotherapy.