Fatal and near-fatal anaphylaxis: The Allergy-Vigilance® Network data (2002-2020).

BACKGROUND: Having a better understanding of the risk factors of severe anaphylaxis is a crucial challenge for physicians. METHODS: To retrospectively analyse fatal/near-fatal anaphylaxis cases recorded by the Allergy-Vigilance® Network (2002-2020) and evaluate the characteristics associated with survival, age and allergens. RESULTS: Among the 3510 anaphylaxis cases documented in the network, 70 (2%) patients (males: 57%; mean age: 35.4 y) presented grade 4 (Ring-Messmer) anaphylaxis and 25 died (19 food-related); 33% had a history of asthma. The main allergens were food (60%; peanut, 20%; milks, 11%) involved in 25/26 cases in children and in 17/44 (39%) cases in adults. Non-food anaphylaxis was related to drugs/latex (24%; neuromuscular blocking agents, 10%; betalactamins, 6%), Hymenoptera (16%). Three food-related cases (one death) occurred during oral food challenge in children. Patients with a food allergy were younger (22.2 years vs. 55 years, p < .001), had more likely a history of asthma (50% vs. 7%; p < .001), a pre-existing allergy (62% vs. 18%; p < .001) compared with other allergies. A cofactor was identified in 35 cases (50%) but predominantly in adults as opposed to children (64% vs. 27%; p = .01). The patients who died were younger (25.6 vs. 40.8 years; p = .01) than the survivors and mostly presented bronchospasm (56% vs. 29%; p = .05). Gaps in the prevention and management of anaphylaxis were noted in 15 cases (21%). CONCLUSIONS: Severe food anaphylaxis has specific features compared with other causes such as young age, asthma history and exercise. Food is also involved in severe anaphylaxis in adults that should not be underestimated.

Relevance of sensitization to legumes in peanut-allergic children.

BACKGROUND: Legume consumption has increased during the two past decades. In France, legumes are responsible for 14.6% of food-related anaphylaxis in children, with peanut as the main allergen (77.5%). Few studies have demonstrated cross-reactivities between peanut and other legumes. The aim of this study was to determine prevalence and relevance of sensitization to legumes in peanut-allergic children. METHODS: All children, aged of 1-17 years, admitted to the Pediatric Allergy Department of the University Hospital of Nancy between January 1, 2017 and February 29, 2020 with a confirmed peanut allergy (PA) and a documented consumption or sensitization to at least one other legume were included. Data were retrospectively collected regarding history of consumption, skin prick tests, specific immunoglobulin E (IgE), prior allergic reactions, and oral food challenges for each legume. RESULTS: Among the 195 included children with PA, 122 were sensitized to at least one other legume (63.9%). Main sensitizations were for fenugreek (N = 61, 66.3%), lentil (N = 38, 42.2%), soy (N = 61, 39.9%), and lupine (N = 63, 34.2%). Among the 122 sensitized children, allergy to at least one legume was confirmed for 34 children (27.9%), including six children who had multiple legume allergies (4.9%). Lentil, lupine, and pea were the main responsible allergens. Half of allergic reactions to legumes other than peanut were severe. CONCLUSION: The high prevalence of legume sensitization and the frequent severe reactions reported in children with PA highlight that tolerated legume consumption should be explored for each legume in the case of PA, and sensitization should be investigated if not.

Food-induced anaphylaxis in infancy compared to preschool age: A retrospective analysis.

OBJECTIVE: Little is known regarding food anaphylaxis in infancy. We aimed to describe specificities of food anaphylaxis in infants (≤12 months) as compared to preschool children (1-6 years). METHODS: We conducted a retrospective study of all food anaphylaxis cases recorded by the Allergy Vigilance Network from 2002 to 2018, in preschool children focusing on infants. RESULTS: Of 1951 food anaphylaxis reactions, 61 (3%) occurred in infants and 386 (20%) in preschool children. Two infants had two anaphylaxis reactions; thus, we analyzed data among 59 infants (male: 51%; mean age: 6 months [SD: 2.9]); 31% had a history of atopic dermatitis, 11% of previous food allergy. The main food allergens were cow's milk (59%), hen's egg (20%), wheat (7%) and peanut (3%) in infants as compared with peanut (27%) and cashew (23%) in preschool children. Anaphylaxis occurred in 28/61 (46%) cases at the first cow's milk intake after breastfeeding discontinuation. Clinical manifestations were mainly mucocutaneous (79%), gastrointestinal (49%), respiratory (48%) and cardiovascular (21%); 25% of infants received adrenaline. Hives, hypotension and neurologic symptoms were more likely to be reported in infants than in preschool children (P = .02; P = .004; P = .002, respectively). Antihistamines and corticosteroids were more often prescribed in preschool children than in infants (P = .005; P = .025, respectively). CONCLUSION: Our study found that in infants presenting with their first food allergy, in a setting with a high rate of infant formula use, the most predominant trigger was cow's milk. As compared to older preschool children, hives, hypotonia and hypotension were more likely to be reported in infants. We believe that this represents a distinct food anaphylaxis phenotype that can further support developing the clinical anaphylaxis criteria in infants.

Predictive factors of allergy to pistachio in children allergic to cashew nut.

BACKGROUND: Cashew nut (CN) allergy prevalence has increased over the last few years. In children allergic to CN, complete avoidance of pistachio is usually recommended, but recent study showed that only one third of children allergic to CN were also allergic to pistachio. The aim of our study was to identify predictive factors of allergy to pistachio in children allergic to CN. METHODS: All children who had a positive oral food challenge (OFC) to CN between November 2013 and October 2017 in the Paediatric Allergy Department of the University Hospital of Nancy were included. Logistic regression models were used to predict the probability of allergy to pistachio. RESULTS: Among the 147 children included, tolerance or allergy to pistachio was known for 51. Out of these, 40 were allergic to pistachio (78.4%). Children allergic to pistachio had a larger weal size of skin prick test to CN (P = .01) and pistachio (P = .0007) and a lower reaction dose to CN (P < .0001). In multivariate analysis, only the reaction dose to CN was significantly associated with allergy to pistachio. Children with a low reaction dose to CN were significantly more at risk to have an allergy to pistachio (P = .01). CONCLUSION: A low reaction dose to CN seems to be a predictive factor of allergy to pistachio in children allergic to CN. In order to limit unnecessary food eviction, a pistachio OFC should be performed in children having high reaction dose whatever the importance of the skin or the specific IgE sensitization to pistachio.

Hydrolyzed Rice Protein-Based Formulas, a Vegetal Alternative in Cow's Milk Allergy.

Formulas adapted to infant feeding, although most of the time made from cow's milk proteins, can be made from hydrolyzed rice protein but they must be classified as "formulas for specific medical needs", according to European regulations. The nutritional quality of rice proteins is thus suitable to be used in infant formulas giving that it is supplemented by certain amino acids which can be lacking. Besides, hydrolysis is required to facilitate their water solubility and digestibility. Owing to a low allergenicity of rice and to the absence of the cross-allergy between milk proteins and rice proteins, these formulas are adapted to the diet of children with cow's milk protein allergy (CMPA), which explains their growing use in some countries. However, CMPA, an expanding disorder, has consequences for growth, bone mineralization, and often has an association with allergy to other foods, including cow's milk extensive hydrolysate, so that a surveillance of the adaption of hydrolyzed rice protein formulas (HRPF) to CMPA, the absence of unexpected side effects, and the appropriate response to its various health hazards seems mandatory. This paper analyses the health problem deriving from CMPA, the industrial development of hydrolyzed rice protein formulas, and the limited number of clinical studies, which confirms, at the moment, a good allergic tolerance and safety. The goal is to better advise heath care professionals on their use of HRPFs during CMPA.

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow's milk.

BACKGROUND: Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow's milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature. METHODS: Children with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food challenge. Blood samples were collected before the challenge. Total and specific levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and to their gastroduodenal digestion products were measured in plasma, using plasma from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional controls. Cytokine secretion and cellular proliferation were analyzed after stimulation of PBMC with different CM allergens. Metabolomic profiles were obtained for plasma samples using liquid chromatography coupled to high-resolution mass spectrometry. RESULTS: Nine children with CM-FPIES and 12 control subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total Ig concentrations were lower than in control subjects, specific Ig against CM components were weak to undetectable, and no specific IgE against CM digestion products were detected. Moreover, in CM-FPIES patients, we did not find any Th cell proliferation or associated cytokine secretion after allergen reactivation, whereas such responses were clearly found in children with IgE-CMA. Plasma metabolic profiles were different between CM allergic patients, with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM-FPIES compared to IgE-CMA patients. CONCLUSIONS: In CM-FPIES, both humoral and cellular specific immune responses are weak or absent, and this is not related to CM avoidance. A metabolomic signature was identified in patients with CM-FPIES that may be useful for the diagnosis and management of this disease.