Food-dependent, exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening disorder that often occurs with exercise, and patients typically have eaten a specific food within hours before disease onset. This disease is exceedingly rare, with a prevalence of 0.02%. No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly. Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years. As the anaphylactic symptoms had not been controlled after traditional treatments, the patient was given subcutaneous injection of dupilumab seven times within 33 weeks. During dupilumab treatments, the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis. Thus, Dupilumab may improve the allergic reactions in FDEIA patients.
Male ; Humans ; Child ; Anaphylaxis/etiology* ; Food Hypersensitivity/diagnosis* ; Exercise-Induced Allergies ; Antibodies, Monoclonal, Humanized/therapeutic use*

BACKGROUND: Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. METHODS: We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children's Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. RESULTS: Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028-1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149-2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094-1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; four or five vaccines vs. a single vaccine). CONCLUSIONS: Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. TRIAL REGISTRATION UMIN000030786 .
Asthma ; epidemiology ; etiology ; Cohort Studies ; Dermatitis, Atopic ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; epidemiology ; etiology ; Humans ; Hypersensitivity ; epidemiology ; etiology ; Infant ; Infant, Newborn ; Japan ; Male ; Vaccines, Inactivated ; adverse effects ; Viral Vaccines ; adverse effects

Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; Chronic Disease ; Cytokines ; Depressive Disorder, Major ; blood ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; blood ; complications ; Histamine ; blood ; Homocysteine ; blood ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; immunology ; Inflammation Mediators ; blood ; Male ; Risk Factors ; S100 Calcium Binding Protein beta Subunit ; blood ; Young Adult

OBJECTIVETo establish a food allergy model in Brown Norway (BN) rats by gavage of ovalbumin (OVA) without any adjuvant, and to evaluate this model.

METHODSA total of 20 male BN rats aged 3 weeks were randomly divided into allergy group and control group (n=10 each). BN rats in the allergy group were given OVA 1 mg per day by gavage, and all the rats were treated for 41 days continuously. On day 42, the rats in the allergy group were given OVA 100 mg by gavage for challenge. The rats in the control group were given normal saline of the same volume by gavage. Differences in body length, body weight, and food intake were compared between the two groups on days 7, 14, 21, 28, 35, and 42. ELISA was used to measure the serum OVA-IgE level and plasma histamine level after challenge on day 42, and the changes in rats' appearance and fecal properties were observed. The model of food allergy was considered successful when the serum OVA-IgE level in the allergy group was no less than the mean serum OVA-IgE level + 3 standard deviation in the control group.

RESULTSThere were no significant differences in body length, body weight or food intake between the allergy and control groups at all time points (P>0.05). On day 21, the control group had a significantly higher food intake than the allergy group (P<0.05). On day 42 after challenge, the allergy group showed significantly higher serum OVA-IgE and plasma histamine levels than the control group (P<0.05). The sensitization rate (rate of successful modeling) was 90%. The fecal properties showed no significant differences between the two groups.

CONCLUSIONSOVA by gavage without any adjuvant can successfully establish the model of food allergy in BN rats and has a high success rate. Food allergy induced by OVA may reduce food intake within a short period of time, but no influence on rats' body length or body weight has been observed.

Animals ; Disease Models, Animal ; Food Hypersensitivity ; etiology ; immunology ; Histamine ; blood ; Immunoglobulin E ; blood ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Inbred BN

: Anaphylaxis is a predominantly childhood disease. Most of the literature on anaphylaxis has emerged from Western countries. This study aimed to describe the incidence, triggers and clinical presentation of anaphylaxis among children in Singapore, look for predictors for anaphylaxis with severe outcomes, and study the incidence of biphasic reactions.: We retrospectively reviewed records of children presenting with anaphylaxis to our paediatric emergency department from 1 January 2007 to 31 December 2014.: We identified 485 cases of anaphylaxis in 445 patients. Cutaneous symptoms (urticarial/angio-oedema) were the most common across all age groups (481 cases, 99%), followed by respiratory (412, 85%), gastrointestinal (118, 24%) and cardiovascular (35, 7.2%) symptoms. Central nervous system symptoms (drowsiness/ irritability) were rare across all age groups (11, 2.2%). Food was identified as the most common trigger across all age groups (45% to 63%). Seafood was the most common food trigger (57, 25%). A total of 420 (86.6%) children were treated with adrenaline, 451 (93%) received steroids and 411 (85%) received antihistamines. Sixty-three (13%) children fulfilled the criteria of severe anaphylaxis. There was no statistically significant association between severe anaphylaxis and the type of trigger (= 0.851), nor an overall past history of atopy (= 0.428). The only independent predictor for severe anaphylaxis was a previous drug allergy (= 0.016). A very low prevalence of biphasic reactions (0.6% of study population) was noted in our study.: We described the presentation and management of anaphylaxis in the Singapore population. A history of drug allergy is associated with severe presentation. Biphasic reactions are rare in our population.
Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Anaphylaxis ; drug therapy ; epidemiology ; etiology ; physiopathology ; Angioedema ; epidemiology ; etiology ; physiopathology ; Child ; Child, Preschool ; Drug Hypersensitivity ; epidemiology ; Emergency Service, Hospital ; Epinephrine ; therapeutic use ; Female ; Food Hypersensitivity ; complications ; epidemiology ; Gastrointestinal Diseases ; epidemiology ; etiology ; physiopathology ; Histamine Antagonists ; therapeutic use ; Humans ; Hypotension ; etiology ; physiopathology ; Incidence ; Infant ; Male ; Pediatrics ; Prevalence ; Respiratory Tract Diseases ; epidemiology ; etiology ; physiopathology ; Retrospective Studies ; Risk Factors ; Seafood ; Severity of Illness Index ; Singapore ; epidemiology ; Sympathomimetics ; therapeutic use ; Tertiary Care Centers ; Urticaria ; epidemiology ; etiology ; physiopathology

Boiled silkworm pupa is a traditional food in Asia, and patients with silkworm pupa food allergy are common in these regions. Still now only one allergen from silkworm, arginine kinase, has been identified. The purpose of this study was to identify novel food allergens in silkworm pupa by analyzing a protein extract after heat treatment. Heat treated extracts were examined by proteomic analysis. A 27-kDa glycoprotein was identified, expressed in Escherichia coli, and purified. IgE reactivity of the recombinant protein was investigated by ELISA. High molecular weight proteins (above 100 kDa) elicited increased IgE binding after heat treatment compared to that before heat treatment. The molecular identities of these proteins, however, could not be determined. IgE reactivity toward a 27-kDa glycoprotein was also increased after heating the protein extract. The recombinant protein was recognized by IgE antibodies from allergic subjects (33.3%). Glycation or aggregation of protein by heating may create new IgE binding epitopes. Heat stable allergens are shown to be important in silkworm allergy. Sensitization to the 27-kDa glycoprotein from silkworm may contribute to elevation of IgE to silkworm.
Adolescent ; Adult ; Allergens/*chemistry/*immunology ; Amino Acid Sequence ; Animals ; Bombyx/*chemistry/genetics/growth & development/*immunology ; Epitopes/immunology ; Female ; Food Hypersensitivity/etiology ; Glycoproteins/*chemistry/genetics/*immunology ; Hot Temperature ; Humans ; Immunoglobulin E/immunology ; Male ; Molecular Sequence Data ; Molecular Weight ; Proteomics ; Pupa/chemistry/immunology ; Recombinant Proteins/biosynthesis/chemistry/immunology ; Sequence Alignment

Food allergy is defined as abnormal immune response elicited by food intake, in which a variety of clinical symptoms will appear as a result of physiological dysfunction and/or tissue damage. Possible mechanisms for food allergy include gastrointestinal tract barrier damage, failure to induce oral immune tolerance, intrauterine sensitization, and allergen transmission during pregnancy and breastfeeding. Hereditary and environmental factors can also contribute to the disease. Gastrointestinal disorders are the main clinical manifestations of the disease. However, hypoalbuminemia, growth retardation, and even acute circulatory failure or shock may occur in severe cases. Oral food challenges are the "gold standard" for the diagnosis of food allergy. Avoidance and replacement of the responsible food are the only effective treatment options for neonatal food allergy. The use of probiotics can offer protection against the disease.
Food Hypersensitivity ; classification ; diagnosis ; etiology ; therapy ; Humans ; Infant, Newborn ; Milk Hypersensitivity ; diagnosis ; etiology ; therapy

OBJECTIVETo measure the prevalence, the possible causes and the influencing factors of allergy, food hypersensitivity and food intolerance in 0-36 month old infants in 8 cities in China.

METHODTotally 2632 infants from the outpatient departments of prevention and health care of two representative hospitals in 8 Chinese cities were randomly selected by applying multistage cluster sampling method from October 2011 to March 2012, and a one-on-one survey to infants' parents was conducted to investigate infants' sensitization status.

RESULTSelf-reported infant allergy rate was 17.97% (473/2632) ; self-reported food hypersensitivity and food intolerance rates were 6.53% (172/2632) and 4.26% (112/2632) , respectively. The proportion of self-reported food hypersensitivity of 0-12 months old infants was 4.47% (74/1656) and their top five allergens in a descending order were eggs (28.38%) , shrimp (25.68%) , fish (21.62%) , milk (18.92%) and wheat (4.05%) . The proportion of self-reported 13-36 months old infant's food hypersensitivity was 10.05% (98/976) . The top five allergens were shrimp (33.93%) , fish (26.79%) , eggs (23.21%) , milk (12.50%) and soy (3.57%) in 13-24 months group, while fish (38.24%) , shrimp (35.29%) , eggs (20.59%) , milk (20.59%) and peanuts (2.94%) in 25-36 months group. Both 7-12 and 13-24 month old were the highest incidence (both of them were 11.98%, 58/484) of age for developing food hypersensitivity and 7-12-month old was also the highest incidence (8.47%, 41/484) of age for food intolerance. The self-reported food intolerance rate was 3.68% (61/1656) and 5.23% (51/976) in the two age groups, respectively. Age, parental history of allergy and father's educational level (OR was 2.452, 1.482 and 2.598, respectively, P < 0.01) were the risk factors of food hypersensitivity; within two weeks of sickness (OR = 1.267, P < 0.05) was the risk factor of food intolerance.

CONCLUSIONInfancy was the most vulnerable period of life of getting allergy, therefore, it is necessary for all infants to prevent allergy through a variety of effective strategies.

Age Distribution ; Child, Preschool ; China ; epidemiology ; Dietary Proteins ; adverse effects ; Egg Hypersensitivity ; epidemiology ; etiology ; Eggs ; adverse effects ; Female ; Food Hypersensitivity ; epidemiology ; etiology ; prevention & control ; Humans ; Incidence ; Infant ; Infant Food ; adverse effects ; Infant Formula ; Infant, Newborn ; Male ; Milk Hypersensitivity ; epidemiology ; etiology ; prevention & control ; Risk Factors ; Sampling Studies ; Sex Distribution ; Surveys and Questionnaires

OBJECTIVETo explore the effect of food allergy (FA) on the development of visceralgia sensibility and the substance P (SP) expression in colon of developing rats with FA.

METHODThree-week old female Sprague-Dawley (SD) rats were randomly divided into two groups (n = 10 in each). The rats in FA group were sensitized with ovalbumin (OVA) 40 µg and Al(OH)3 1 mg suspension solution (0.2 ml) intraperitoneal (i.p.) injection on day 0, only OVA 40 µg solution i.p. on day 2, 4, 7, 9, 11, respectively, and the rats were challenged by gavage with OVA solution 30 mg (2 ml) on day 20, 24, 28, 30. The rats in non-sensitized (NS) group were not challenged except handled in the same ways. The serum OVA-IgE were determined by enzyme-linked immuno sorbent assay (ELISA) on day 0, 30. Jejunum segments were used to observe morphological structure, the expression of eosinophils, and the density and the percentage of degranulation of mast cells (MC). The rats were appraised for the pain sensibility of intestinal tract under colorectal distension irritation by the electrophysiological method on external oblique in the 18-24 hr after the last challenge. Colons were used to analyze the expression of SP through immunohistochemical staining and computer image analyzing system.

RESULTThe serum OVA-IgE concentration and the eosinophils, mast cell, the percentage of mast cells degranulation in FA group were more than NS group (P < 0.01). The amplitudes of spike external oblique muscle of abdomen (EOMA, µV) of the FA group under the colorectal distension (CRD) pressures at 0, 15, 30, 45, 60, 75 mm Hg were (17.74 ± 0.72), (18.63 ± 1.72), (22.55 ± 1.70), (28.63 ± 7.00), (33.97 ± 7.34), (37.26 ± 8.40), and (17.43 ± 1.18), (17.27 ± 1.16), (17.73 ± 1.42), (19.55 ± 3.54), (23.29 ± 5.46), (25.20 ± 4.75) in NS group. With the CRD pressure increased, the amplitudes of spike EOMA increased significantly. There were significant differences between groups under the CRD pressures at 30, 45, 60, 75 mm Hg (F = 47.470, 13.367, 13.317, 15.390, P < 0.01). The expressions of colons SP in FA group and NS group are 247.12 ± 90.83 and 103.90 ± 58.94, respectively (t = 4.183, P < 0.01).

CONCLUSIONSensitization through i.p. pathway and challenge by gavage with OVA in early life could result in FA in young SD rats. FA in early life enabled the amplitudes of spike EOMA and the expression of colons SP increase significantly. It may be related to increase in amount and degranulation of MC and SP abnormal expression in colon, which could lead to the development of visceralgia sensibility.

Animals ; Colonic Diseases, Functional ; metabolism ; Disease Models, Animal ; Electrophysiology ; Female ; Food Hypersensitivity ; complications ; metabolism ; Hyperalgesia ; etiology ; metabolism ; physiopathology ; Intestinal Mucosa ; metabolism ; pathology ; Mast Cells ; metabolism ; Ovalbumin ; adverse effects ; Pain Threshold ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological ; Substance P ; metabolism

The aim of this study was to analyze the natural history of atopic dermatitis (AD) and the risk factors associated with the remission of AD in Korean children. We enrolled 597 children with AD that occurred in the first year of life. A variety of factors influencing the prognosis were assessed by medical records and telephone interviews. Their outcome was classified into complete remission, intermittent, and persistent AD. AD had completely disappeared in 422 cases (70.6%), while 149 (25%) and 26 cases (4.4%) showed intermittent and persistent skin symptoms, respectively. The average healing time was 29.6 months in complete remission group and expected healing time of the AD was 60 months. None of risk factors were significant by multivariate analysis. But, in moderate-to-severe AD group, maternal diet restriction during lactation (P = 0.046) and no sensitization to cow's milk (P = 0.017) were significantly associated with remission of AD in the multivariate analysis. In conclusion, AD occurring in the first year of life disappears in a significant proportion of patients. In addition, in Korean children with moderate-to-severe AD, maternal diet restriction of allergenic food during lactation and sensitization to cow's milk seem to predict the prognosis of AD.
Adult ; Child, Preschool ; Dermatitis, Atopic/*diagnosis/etiology ; Female ; Food Hypersensitivity/complications ; Humans ; Infant ; Interviews as Topic ; Lactation ; Male ; Milk Hypersensitivity/complications ; Predictive Value of Tests ; Prognosis ; Remission Induction ; Republic of Korea ; Retrospective Studies ; Risk Factors