Increasing emergency department visits for anaphylaxis in very early childhood: A canary in the coal mine.

AIM: The incidence of anaphylaxis is increasing globally in tandem with changing environmental and lifestyle factors. There is very limited data on very early childhood presentations. We aim to assess changes in rates, characteristics and management of infant anaphylaxis in a paediatric ED over a 15-year period. METHODS: We conducted a retrospective study of children <2 years of age who presented with verified anaphylaxis comparing cases in years 2003-2007 with those in 2013-2017. Standardised information was collected on demographics, clinical presentation, management and triggers. RESULTS: Manually confirmed anaphylaxis rates in <2 year olds increased from 3.6 to 6.2 per 104 population (OR 1.7, 95% CI: 1.3-2.7; p < 0.001) with the greatest increase in <1 year olds. Anaphylaxis severity increased between 2003-2007 and 2013-2017 (OR 2.3, 95% CI: 1.2-4.3; p = 0.018). Failure to administer adrenaline was reduced in 2013-2017 (p = 0.007). Food was the leading anaphylaxis trigger (97.85%). CONCLUSION: This is the first study to suggest an increase in the incidence and severity of ED anaphylaxis presentations in children aged <2 years. Increased awareness of specific characteristics in this age group is required to facilitate timely recognition and optimal management. Further large-scale studies are warranted to understand underlying environmental drivers and find prevention strategies to reduce the burden of disease.

Pre- and Postnatal Vitamin D Status and Allergy Outcomes in Early Childhood.

The dramatic increase in the prevalence of allergic disease in recent decades reflects environmental and behavioural changes that have altered patterns of early immune development. The very early onset of allergic diseases points to the specific vulnerability of the developing immune system to environmental changes and the development of primary intervention strategies is crucial to address this unparalleled burden. Vitamin D is known to have immunomodulatory functions. While allergic disease is multifactorial, associations with reduced sunlight exposure have led to the hypothesis that suboptimal vitamin D levels during critical early periods may be one possible explanation. Interventions to improve vitamin D status, especially in early life, may be the key to allergic disease prevention.

Acute management of anaphylaxis in pregnancy.

BACKGROUND: Anaphylaxis in pregnancy is rare but can potentially be associated with significant morbidity and mortality for the mother, fetus and neonate. With appropriate and timely management, even severe anaphylaxis can be managed with excellent maternal and fetal outcomes. OBJECTIVE: The aim of this article is to provide an illustrative case and highlight current recommendations for diagnosis and management of acute maternal anaphylaxis, which have recently been reviewed and developed into a guideline by the Australasian Society of Clinical Immunology and Allergy. DISCUSSION: An understanding of management of anaphylaxis in pregnancy is essential knowledge in the general practice setting. The recommended dosage and administration of adrenaline (epinephrine) for anaphylaxis is the same in pregnant and non-pregnant patients: 0.5 mg adrenaline intramuscularly in the mid-outer thigh (or dose of 0.01 mg/kg if <50 kg). The use of adrenaline in maternal anaphylaxis is supported by various international guidelines.

Penicillin allergy SHACK: Survey of hospital and community knowledge.

AIM: Penicillin allergy accounts for the majority of all reported adverse drug reactions in adults and children. Foregoing first-line antibiotic therapy due to penicillin allergy label is associated with an increased prevalence of infections by resistant organisms and longer hospitalisation. Clinician awareness of allergy assessment, referral indications, management of allergy and anaphylaxis is therefore vital but globally lacking. We aim to assess the knowledge of penicillin allergy, assessment and management in Western Australian health professionals. METHODS: An anonymous survey was distributed to pharmacists, nurses and physicians within Western Australian paediatric and adult Hospitals, Community and General Practice. RESULTS: In total, 487/611 were completed and included in the statistical analysis. Only 62% (301/487) of respondents routinely assessed for patient medication allergies. Of those who assessed allergy, 9% (28/301) of respondents met the Australian standards for allergy assessment. Only 22% (106/487) of participants correctly cited all indications for management with adrenaline in anaphylaxis to antibiotics and 67% (197/292) of physicians rarely or never referred to an allergy service. Paediatric clinicians had an increased understanding of allergy assessment and anaphylaxis management. Recent penicillin allergy education within a 5-year period led to significant improvements in allergy knowledge. CONCLUSION: Overall, knowledge, assessment and management of penicillin allergies among practitioners in Western Australia are currently inadequate in adults and paediatric clinicians to provide safe and effective clinical care. The implementation of a targeted education program for WA health professionals is urgently required and is expected to improve clinician knowledge and aid standardised penicillin assessment (de-labelling) practices.

The Influence of Sunlight Exposure and Sun Protecting Behaviours on Allergic Outcomes in Early Childhood.

The dramatic rise in allergic disease has occurred in tandem with recent environmental changes and increasing indoor lifestyle culture. While multifactorial, one consistent allergy risk factor has been reduced sunlight exposure. However, vitamin D supplementation studies have been disappointing in preventing allergy, raising possible independent effects of ultraviolet (UV) light exposure. The aim of this study was to examine whether UV light exposure influences the development of allergic disease in early childhood. Direct sunlight exposure (290-380 nm) in early infancy was measured via UV dosimeters. Outdoor exposure, sun protective behaviours, and allergy outcomes were assessed over the first 2.5 years of life with clinical assessment appointments at 3, 6, 12 and 30 months of age. Children with eczema had less (p = 0.038) direct UV light exposure between 0-3 months of age (median (IQR) 747 (473-1439) J/m2) than children without eczema (median (IQR) 1204 (1717-1843) J/m2); and less outdoor exposure time (7 min/day) between 11 a.m. and 3 p.m. compared to children without eczema (20 min/day, p = 0.011). These associations were seen independent of vitamin D status, and after adjusting for other potential confounders. Whilst we could not find any associations between direct UV light exposure and other allergic disease outcomes, exposure to UV light appears to be beneficial in reducing the risk of eczema development in early childhood. Further research is required to determine optimal levels of UV light exposure while balancing the potential risks.

In "High-Risk" Infants with Sufficient Vitamin D Status at Birth, Infant Vitamin D Supplementation Had No Effect on Allergy Outcomes: A Randomized Controlled Trial.

Lower vitamin D status at birth and during infancy has been associated with increased incidence of eczema and food allergies. The aim of this study was to investigate the effect of early infancy vitamin D supplementation on allergic disease outcomes in infants at "hereditary risk" of allergic disease, but who had sufficient vitamin D levels at birth. Here, we report the early childhood follow-up to 2.5 years of age of "high-risk" infants who participated in a double-blinded, randomized controlled trial. For inclusion in this trial, late gestation (36-40 weeks) maternal 25-hydroxyvitamin D levels needed to be ≥50 nmol/L. Infants were randomized to either oral vitamin D supplementation of 400 IU/day (n = 97) or a placebo (n = 98) for the first six months of life. Vitamin D levels and allergic disease outcomes were followed up. There were no statistically significant differences in incidence of any medically diagnosed allergic disease outcomes or allergen sensitization rates between the vitamin D-supplemented and placebo groups at either 1 year or at 2.5 years of age. In conclusion, for "allergy high-risk" infants who had sufficient vitamin D status at birth, early infancy oral vitamin D supplementation does not appear to reduce the development of early childhood allergic disease.

In infants with sufficient vitamin D status at birth, vitamin D supplementation does not impact immune development.

BACKGROUND: Low vitamin D levels have been associated with allergic diseases. Vitamin D has potent immunomodulatory properties, but the mechanisms remain unclear. We have investigated the effect of oral vitamin D supplementation on circulating immune cell phenotypes in infants. METHOD: A double-blinded randomised controlled trial was conducted to investigate the effect of oral vitamin D supplementation (400 IU/d) on eczema and immune development. A subset of 78 infants was included in this analysis. Phenotypic analysis of immune cell subsets was performed using flow cytometry. RESULTS: Vitamin D supplementation resulted in median 25(OH)D levels of 80.5 vs 59.5 nmol/L in the placebo group at 3 months of age (P = .002) and 87.5 vs 77 nmol/L at 6 months of age (P = .08). We observed significant changes in immune cell composition from birth (cord blood) to 6 months of age. Vitamin D supplementation did not impact these changes, nor did immune cell composition correlate with plasma 25(OH)D levels. Through exploratory analysis, we identified possible associations with eczema development and increased abundance of naïve CD4- T cells at birth, as well as associations with basophils, iNKT and central memory CD4+ T cells, and altered expression patterns of IgE receptor (FcεR1) on monocytes and dendritic cells with eczema at 6 months. CONCLUSIONS: Vitamin D supplementation in infants who were vitamin D sufficient at birth did not affect developmental changes in immune cells during the first 6 months of life. However, immune cell profiles at birth and at 6 months of age were associated with early life eczema.

Analytical Bias in the Measurement of Plasma 25-Hydroxyvitamin D Concentrations in Infants.

Hypovitaminosis D is prevalent worldwide; however, analytical bias in the measurement of circulating 25-hydroxyvitamin D (25(OH)D) concentrations may affect clinical treatment decisions and research. We performed parallel plasma 25(OH)D analyses using the Abbott Architect i2000 chemiluminescent immunoassay (CIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for paired samples from the same infants at 3 (n = 69), 6 (n = 79) and 12 months (n = 73) of age. To test agreement, we used Lin's concordance correlation coefficient and corresponding 95% confidence interval, Bland-Altman's limits of agreement, and Bradley-Blackwood (BB) test. Agreement was high at 3 months (coefficient between difference and mean -0.076; BB F = 0.825; p = 0.440), good at 12 months (-0.25; BB F = 2.41; p = 0.097) but missing at 6 months of age (-0.39; BB F = 12.30; p < 0.001). Overall, 18 infants had disparate results based on the cut-off point for vitamin D deficiency (25(OH)D < 50 nmol/L), particularly at three months, with seven (10%) infants deficient according to CIA but not LC-MS/MS, and four (6%) deficient by LC-MS/MS but not CIA. To our knowledge, this is the first study to show that the reported 25(OH)D concentration may be influenced by both age and assay type. Physicians and researchers should be aware of these pitfalls when measuring circulating 25(OH)D concentrations in infants and when developing treatment plans based on measured vitamin D status.

The role of skin testing and extended antibiotic courses in assessment of children with penicillin allergy: An Australian experience.

AIM: To determine if skin testing (ST) in addition to extended oral provocation challenge (OPC) is necessary for beta-lactam allergy verification in an Australian paediatric population. METHODS: This was a retrospective study (176 children) that undertook assessments for beta-lactam allergy from 2006 to 2015 at a tertiary paediatric hospital. Patients either underwent direct OPC without ST or ST plus challenge if ST was negative. RESULTS: The analysis included children with a history of varying rash types/severity as well as angioedema and reported anaphylaxis. A direct OPC was undertaken in 73 children. Three children reacted with one anaphylaxis. A total of 103 children underwent ST, with 13 children (12.6%) reacting. Of the 90 who subsequently proceeded to OPC, 4 reacted. A total of 132 children were given an extended oral course of the culprit antibiotic, to which 6 children reacted. CONCLUSIONS: A direct OPC with the culprit drug in Australian children can be safely performed, avoiding resource-intensive and painful ST. Our data demonstrate that a prior history of anaphylaxis does not necessarily predict IgE-mediated allergy, as detected by positive immediate ST or reactions to oral challenge. Such history should not detract from efforts to assess these children for antibiotic allergy. We suggest that extended courses of at least 5 days are important in paediatric antibiotic de-labelling as six children (4.5% of those who were prescribed the extended course) reacted in our study and even developed symptoms late in the extended course, from days 2 to 6.

Antibiotic Allergy Labels in Children Are Associated with Adverse Clinical Outcomes.

BACKGROUND: Self-reported antibiotic allergies are common among hospitalized adults and children. However, there is a paucity of studies investigating the impact of an antibiotic allergy label in childhood. OBJECTIVE: To investigate the impact of antibiotic allergy labeling on clinical outcomes in children. METHODS: A retrospective study was conducted in a major pediatric tertiary hospital to capture inpatient admissions (N = 1672) in April 2014 and April 2015. Data, collected by chart review, included documented antibiotic allergy labels, antibiotic prescriptions, admitting specialty, hospital length of stay, and hospital readmissions. RESULTS: Of the 1672 pediatric patients surveyed, 58.1% were male and 44.8% were prescribed antibiotics. Antibiotic allergy labels were recorded in 5.3% of patients; most were ß-lactam allergy labels (85%), mostly to unspecified penicillins. There was an increasing incidence of antibiotic allergy label with age, which was statistically significant (P < .001); no sex effect was seen. Patients with antibiotic allergy labels received more macrolide (P = .045), quinolones (P = .01), lincosamide (P < .001), and metronidazole (P = .009) antibiotics than did patients without an antibiotic allergy label. After adjusting for patient age, sex, principal diagnosis, and admitting specialty, children with any antibiotic or ß-lactam allergy label had longer hospital stays (odds ratio, 1.62; 95% CI, 1.05-2.50; P = .03) with a mean length of hospital stay of 3.8 days for those without a label and 5.2 days for those with a ß-lactam allergy label. CONCLUSIONS: This is the first study demonstrating the negative impact of antibiotic allergy labels on clinical outcomes in children, as evidenced by significant alternate antibiotic use and longer hospital stays.

Direct infant UV light exposure is associated with eczema and immune development.

BACKGROUND: Suboptimal vitamin D levels during critical periods of immune development have emerged as an explanation for higher rates of allergic diseases associated with industrialization and residing at higher latitudes. OBJECTIVE: We sought to determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development. METHODS: By using a double-blind randomized controlled trial, newborn infants were randomized to receive vitamin D supplementation (400 IU/d) or a placebo until 6 months of age. Some infants also wore personal UV dosimeters to measure direct UV light (290-380 nm) exposure. Infant vitamin D levels were measured at 3 and 6 months of age. Eczema, wheeze, and immune function outcomes were assessed at 6 months of age. RESULTS: At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater for the vitamin D-supplemented group than the placebo group, but there was no difference in eczema incidence between groups. Infants with eczema were found to have had less UV light exposure (median, 555 Joules per square meter [J/m2; interquartile range, 322-1210 J/m2]) compared with those without eczema (median, 998 J/m2 [interquartile range, 676-1577 J/m2]; P = .02). UV light exposure was also inversely correlated with IL-2, GM-CSF, and eotaxin production to Toll-like receptor ligands. CONCLUSION: This study is the first to demonstrate an association between greater direct UV light exposures in early infancy with lower incidence of eczema and proinflammatory immune markers by 6 months of age. Our findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life.

Appendicular fracture epidemiology of children and adolescents: a 10-year case review in Western Australia (2005 to 2015).

Fracture incidence data of Australian children and adolescents have not been reported in the literature. A 10-year case review of fracture presentations in Western Australia is provided. Between 2005 and 2015, fracture incidence increased relative to population growth. This is concerning, and interventions are required to reverse this trend. PURPOSE: Fracture incidence in 0-16-year-olds is high and varies between countries. Boys have a 1.5:1 ratio of fracture incidence compared to girls. There are no specific data for Australia. Western Australia is a state with unique geography and population distribution having only a single tertiary paediatric hospital (Princess Margaret Hospital, PMH, in Perth) managing the majority of children and adolescents with fractures in the Emergency Department (ED). The aims of this study were to characterise fracture presentations to PMH-ED and compare the incidence to population data. METHODS: A database audit of fracture presentations between 2005 and 2015 for fracture rates with a sub-analysis for gender, fracture site and age and a comparison to Perth Metropolitan and Western Australian population data was performed. RESULTS: Analysis included 31,340 presentations. Fracture incidence, adjusted for the annual population size, increased from 0.63% in 2005 to 0.85% in 2015 (p < 0.001). The month of May reported the highest fracture rate (p < 0.001) corresponding with the start of the winter sports season. Males had a 1.5 times higher fracture incidence than females (p < 0.001), with upper limb fractures three times more common than lower limb fractures (p < 0.001). Fracture incidence increased with age until the early teenage years (15 years for males; 12 years for females) when a decline occurred. CONCLUSIONS: Increased fracture incidence in Western Australia between 2005 and 2015 identifies a concerning trend for bone health in children and adolescents. Further research is needed to identify potential lifestyle factors that impact fracture incidence translating into evidence-based strategies to reverse these trends and improve bone health.

Increased Use of Adrenaline in the Management of Childhood Anaphylaxis Over the Last Decade.

BACKGROUND: We recently determined that allergy training programs have improved physician recognition and diagnosis of pediatric anaphylaxis in the last decade. OBJECTIVE: To investigate for changes in management, in particular the appropriate use of adrenaline for the treatment of anaphylaxis in a tertiary pediatric emergency department (PED). METHODS: We conducted a retrospective case note study including children aged 0 to 16 years coded and verified for anaphylaxis comparing cases in years 2003/2004 with 2012. This included standardized information on clinical presentation, demographic characteristics, vital signs, mode of transport, and management of anaphylaxis including the use of adrenaline and/or adjunct therapy. Follow-up management plans were also recorded. RESULTS: In 2003/2004, a total of 92 cases were coded and verified for anaphylaxis from 83,832 PED presentations compared with 159 cases from 71,822 PED presentations in 2012. A significantly higher proportion of cases were appropriately managed with adrenaline in 2012 compared with 2003/2004, when intensive training programs had not yet been introduced (P = .03). Vital signs were more frequently documented in 2012 (P < .001) than in 2003/2004, and there was significantly less administration of other medications (corticosteroids, bronchodilators, and antihistamines) (P < .05). Also, changes in discharge management occurred with an improved dispensing/prescription of adrenaline autoinjectors and more frequent follow-up arrangement with specialist allergy services (P < .001). CONCLUSIONS: There was a significant improvement in the management of anaphylaxis over this 10-year period. This change was observed after the introduction of intensified physician training programs in which anaphylaxis management was a key component highlighting the importance of cooperation between pediatric emergency and allergy services.

Developing Primary Intervention Strategies to Prevent Allergic Disease.

Allergic diseases are a major cause of morbidity in the developed world, now affecting up to 40 % of the population with no evidence that this is abating. If anything, the prevalence of early onset allergic diseases such as eczema and food allergy appears to be still increasing. This is almost certainly due to the changing modern environment and lifestyle factors, acting to promote immune dysfunction through early perturbations in immune maturation, immune tolerance and regulation. This early propensity to inflammation may also have implications for the rising risk of other inflammatory non-communicable diseases (NCDs) later in life. Identifying risk factors and pathways for preventing early onset immune disease like allergy is likely to have benefits for many aspects of human health, particularly as many NCDs share similar risk factors. This review focuses on recent advances in primary intervention strategies for promoting early immune health and preventing allergic disease, highlighting the current evidence-based guidelines where applicable and areas requiring further investigation.