Raymond James Mullins

Anaphylaxis: risk factors for recurrence

Background  There are few studies on the incidence or recurrence of anaphylaxis.

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.

Characteristics of childhood peanut allergy in the Australian Capital Territory, 1995 to 2007.

BACKGROUND It is unknown whether clinical features of peanut allergy have changed in the past decade alongside possible increasing prevalence. OBJECTIVE The clinical features of peanut allergy over 13 years were examined with regard to age of onset, sex distribution, severity, and incidence. METHODS Retrospective study of 778 patients (age 4 months to 66 years) diagnosed with peanut allergy at a community-based specialist allergy practice in the Australian Capital Territory. RESULTS Most peanut allergy (90%) developed by age 72 months. In this group, there were no significant time-dependent changes in sex distribution, reaction severity, or age of first reaction (mean/median 12/15.1 months). Later age of first reaction was associated with an increased risk of anaphylaxis in the overall population (P < .01) and in those with onset by 72 months, in whom risk increased by 22.7% (CI, 3.3-45.7) for every additional year of age (P < .02). Asthma was associated with increased risk of anaphylaxis (odds ratio, 1.9; P < .001). In children with peanut allergy, 22% experienced anaphylaxis with first exposure and 30% with anaphylaxis had preceding milder reactions. The estimated minimum incidences of peanut allergy and sensitization by age 72 months for children born in the Australian Capital Territory in 2004 were 1.15% and 1.53%, respectively (by end December 2007), compared with 0.73% and 0.84% for those born in 2001. CONCLUSION Although most characteristics of peanut allergy have changed little over the period of the last 13 years (onset age, sex, comorbidity, severity), later onset was associated with greater risk of anaphylaxis. Our data are consistent with a rise in incidence.

Regional variation in epinephrine autoinjector prescriptions in Australia: more evidence for the vitamin D-anaphylaxis hypothesis.

BACKGROUND There is little information on the regional distribution of anaphylaxis in Australia. OBJECTIVE To examine the influence of latitude (a marker of sunlight/vitamin D status) as a contributor to anaphylaxis in Australia, with a focus on children from birth to the age of 4 years. METHODS Epinephrine autoinjector (EpiPen) prescriptions (2006-2007) in 59 statistical divisions and anaphylaxis hospital admission rates (2002-2007) in 10 regions were used as surrogate markers of anaphylaxis. RESULTS EpiPen prescription rates (per 100,000 population per year) were higher in children from birth to the age of 4 years (mean, 951) than in the overall population (mean, 324). In an unadjusted model of children from birth to the age of 4 years, decreasing absolute latitude was associated with a decrease in EpiPen prescription rates, such that rates were higher in southern compared with northern regions of Australia (beta, -44.4; 95% confidence interval, -57.0 to -31.8; P < .001). Adjusting for age, sex, ethnicity, indexes of affluence, education, or access to medical care (general, specialist allergy, or pediatric) did not attenuate the finding (beta, -51.9; 95% confidence interval, -71.0 to -32.9; P < .001). Although statistical power was limited, anaphylaxis admission rates (most prominent in children aged 0-4 years) showed a similar south-north gradient, such that admission rates were higher in southern compared with northern regions of Australia. CONCLUSIONS EpiPen prescription rates and anaphylaxis admissions are more common in southern regions of Australia. These data provide additional support for a possible role of vitamin D in the pathogenesis of anaphylaxis.

Season of birth and food allergy in children

BACKGROUND The prevalence of food allergy is rising, and etiologic factors remain uncertain. Evidence implicates a role for vitamin D in the development of atopic diseases. Based on seasonal patterns of UV-B exposure (and consequent vitamin D status), we hypothesized that patients with food allergy are more often born in fall or winter. OBJECTIVE To investigate whether season of birth is associated with food allergy. METHODS We performed a multicenter medical record review of all patients presenting to 3 Boston emergency departments (EDs) for food-related acute allergic reactions between January 1, 2001, and December 31, 2006. Months of birth in patients with food allergy were compared with that of patients visiting the ED for reasons other than food allergy. RESULTS We studied 1002 patients with food allergy. Of younger children with food allergy (age < 5 years), but not older children or adults, 41% were born in spring or summer compared with 59% in fall or winter (P = .002). This approximately 40:60 ratio differed from birth season in children treated in the ED for non-food allergy reasons (P = .002). Children younger than 5 years born in fall or winter had a 53% higher odds of food allergy compared with controls. This finding was independent of the suspected triggering food and allergic comorbidities. CONCLUSIONS Food allergy is more common in Boston children born in the fall and winter seasons. We propose that these findings are mediated by seasonal differences in UV-B exposure. These results add support to the hypothesis that seasonal fluctuations in sunlight and perhaps vitamin D may be involved in the pathogenesis of food allergy.

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.

Season of birth and childhood food allergy in Australia

To cite this article: Mullins RJ, Clark S, Katelaris C, Smith V, Solley G, Camargo CA, Jr. Season of birth and childhood food allergy in Australia. Pediatric Allergy Immunology 2011; 22: 583–589.

Regional variation in infant hypoallergenic formula prescriptions in Australia.

Mullins RJ, Clark S, Camargo Jr CA. Regional variation in infant hypoallergenic formula prescriptions in Australia.
Pediatr Allergy Immunol 2010: 21: e413–e420.
© 2009 John Wiley & Sons A/S

Increases in anaphylaxis fatalities in Australia from 1997 to 2013.

Recent epidemiological studies indicate increases in Australian, UK and US hospital anaphylaxis admission rates.

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.