There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World ...Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.
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Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority ...public health issue. However, management of anaphylaxis – both acute and preventative – varies by region.
The World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions.
Responses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis.
This survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.
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While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a ...whole.
To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally.
We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts.
Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”. Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as “strongly agree” to “agree” after the second round. Based on feedback, 2 additional online voting rounds were conducted.
We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score.
The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.
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4.
Reduced Estimated GFR and Cancer Mortality Iff, Samuel, MD; Craig, Jonathan C., MD, PhD; Turner, Robin, PhD ...
American journal of kidney diseases,
01/2014, Volume:
63, Issue:
1
Journal Article
Peer reviewed
Background Chronic kidney disease is associated with an increased risk of cancer, but whether reduced kidney function also leads to increased cancer mortality is uncertain. The aim of our study was ...to assess the independent effects of reduced kidney function on the risk of cancer deaths. Study Design Prospective population-based cohort study. Setting & Participants Participants of the Blue Mountains Eye Study (n = 4,077; aged 49-97 years). Predictor Estimated glomerular filtration rate (eGFR). Outcomes Overall and site-specific cancer mortality. Results During a median follow-up of 12.8 (IQR, 8.6-15.8) years, 370 cancer deaths were observed in our study cohort. For every 10-mL/min/1.73 m2 reduction in eGFR, there was an increase in cancer-specific mortality of 18% in the fully adjusted model ( P < 0.001). Compared with participants with eGFR ≥ 60 mL/min/1.73 m2 , the adjusted HR for cancer-specific mortality for those with eGFR < 60 mL/min/1.73 m2 was 1.27 (95% CI, 1.00-1.60; P = 0.05). This excess cancer mortality varied with site, with the greatest risk for breast and urinary tract cancer deaths (adjusted HRs of 1.99 95% CI, 1.05-3.85; P = 0.01 and 2.54 95% CI, 1.02-6.44; P = 0.04, respectively). Limitations Residual confounding, such as from unmeasured socioeconomic factors and the potential effects of erythropoiesis-stimulating agents on cancer deaths, may have occurred. Conclusions eGFR < 60 mL/min/1.73 m2 appears to be a significant risk factor for death from cancer. These effects appear to be site specific, with breast and urinary tract cancers incurring the greatest risk of death among those with reduced kidney function.
Food protein–induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; ...high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.
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Background Epidemiologic evidence suggests delayed introduction of egg might not protect against egg allergy in infants at risk of allergic disease. Objective We sought to assess whether dietary ...introduction of egg between 4 and 6 months in infants at risk of allergy would reduce sensitization to egg. Methods We conducted a randomized controlled trial in infants with at least 1 first-degree relative with allergic disease. Infants with a skin prick test (SPT) response to egg white (EW) of less than 2 mm were randomized at age 4 months to receive whole-egg powder or placebo (rice powder) until 8 months of age, with all other dietary egg excluded. Diets were liberalized at 8 months in both groups. The primary outcome was an EW SPT response of 3 mm or greater at age 12 months. Results Three hundred nineteen infants were randomized: 165 to egg and 154 to placebo. Fourteen infants reacted to egg within 1 week of introduction (despite an EW SPT response <2 mm at entry) and were unsuitable for intervention. Two hundred fifty-four (83%) infants were assessed at 12 months of age. Loss to follow-up was similar between groups. Sensitization to EW at 12 months was 20% and 11% in infants randomized to placebo and egg, respectively (odds ratio, 0.46; 95% CI, 0.22-0.95; P = .03, χ2 test). The absolute risk reduction was 9.8% (95% CI, 8.2% to 18.9%), with a number needed to treat of 11 (95% CI, 6-122). Levels of IgG4 to egg proteins and IgG4 /IgE ratios were higher in those randomized to egg ( P < .0001 for each) at 12 months. There was no effect on the proportion of children with probable egg allergy (placebo, 13; egg, 8). Conclusions Introduction of whole-egg powder into the diets of high-risk infants reduced sensitization to EW and induced egg-specific IgG4 levels. However, 8.5% of infants randomized to egg were not amenable to this primary prevention.
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Objective Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Guidelines recommend initiating statins early to reduce low-density ...lipoprotein cholesterol (LDL-C). Studies have evaluated rosuvastatin in children aged ≥10 years, but its efficacy and safety in younger children is unknown. Methods Children with HeFH and fasting LDL-C >4.92 mmol/L (190 mg/dL) or >4.10 mmol/L (>158 mg/dL) with other cardiovascular risk factors received rosuvastatin 5 mg daily. Based on LDL-C targets (<2.85 mmol/L <110 mg/dL), rosuvastatin could be uptitrated to 10 mg (aged 6–9 years) or 20 mg (aged 10–17 years). Treatment lasted 2 years. Changes in lipid values, growth, sexual maturation, and adverse events (AEs) were assessed. Results The intention-to-treat analysis included 197 patients. At 24 months, LDL-C was reduced by 43, 45, and 35% vs baseline in patients aged 6–9, 10–13, and 14–17 years, respectively ( P < .001 for all groups). Most AEs were mild. Intermittent myalgia was reported in 11 (6%) patients and did not lead to discontinuation of rosuvastatin treatment. Serious AEs were reported by 9 (5%) patients, all considered unrelated to treatment by the investigators. No clinically important changes in hepatic biochemistry were reported. Rosuvastatin treatment did not appear to adversely affect height, weight, or sexual maturation. Conclusions In HeFH patients aged 6–17 years, rosuvastatin 5–20 mg over 2 years significantly reduced LDL-C compared with baseline. Treatment was well tolerated, with no adverse effects on growth or sexual maturation.
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Background The role of basophils in anaphylaxis is unclear. Objective We sought to investigate whether basophils have an important role in human anaphylaxis. Methods In an emergency department study ...we recruited 31 patients with acute anaphylaxis, predominantly to Hymenoptera venom. We measured expression of basophil activation markers (CD63 and CD203c); the absolute number of circulating basophils; whole-blood FCER1A , carboxypeptidase A3 (CPA3) , and L-histidine decarboxylase (HDC) gene expression; and serum markers (CCL2, CCL5, CCL11, IL-3, and thymic stromal lymphopoietin) at 3 time points (ie, during the anaphylactic episode and in convalescent samples 7 and 30 days later). We recruited 134 patients with Hymenoptera allergy and 76 healthy control subjects for comparison. We then investigated whether the changes observed during venom-related anaphylaxis also occur during allergic reactions to food in 22 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge to peanut. Results The number of circulating basophils was significantly lower during anaphylaxis (median, 3.5 cells/μL) than 7 and 30 days later (17.5 and 24.7 cells/μL, P < .0001) and compared with those in patients with venom allergy and healthy control subjects (21 and 23.4 cells/μL, P < .0001). FCER1A expression during anaphylaxis was also significantly lower than in convalescent samples ( P ≤ .002) and control subjects with venom allergy ( P < .0001). CCL2 levels (but not those of other serum markers) were significantly higher during anaphylaxis (median, 658 pg/mL) than in convalescent samples (314 and 311 pg/mL at 7 and 30 days, P < .001). Peanut-induced allergic reactions resulted in a significant decrease in circulating basophil counts compared with those in prechallenge samples ( P = .016), a decrease in FCER1A expression ( P = .007), and an increase in CCL2 levels ( P = .003). Conclusions Our findings imply an important and specific role for basophils in the pathophysiology of human anaphylaxis.
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