Evaluation of atopic diseases in patients with allergic contact dermatitis.

Background: There is controversy on whether allergic contact dermatitis (ACD) is associated with atopy. Research on eczema and the risk of ACD is mixed, and there is sparse literature on other atopic conditions. Objective: Our study examined the prevalence of several atopic conditions, including allergic rhinitis, eczema, asthma, and food allergies in patients with ACD, and compared these to patients without ACD. Methods: We retrospectively reviewed adult patients ages ≥ 18 years with ACD (n = 162) with positive patch testing results and documented any history of atopy, including childhood eczema, asthma, allergic rhinitis, and immunoglobulin E-mediated food allergy. The prevalence of atopic conditions was compared between our ACD cohort and controls without ACD (n = 163) from our electronic medical records system (age and gender matched). Results: Among our patients with ACD, 53 (33%) had allergic rhinitis, 22 (14%) had childhood eczema, 32 (20%) had asthma, and 8 (5%) had food allergies. We observed that the odds of atopy overall (n = 76) in the ACD group compared with the control group were increased (odds ratio [OR] 1.88; p = 0.007). Allergic rhinitis was the highest risk factor (n = 53) with an OR of 12.64 (p < 0.001). Childhood eczema (n = 22) was also increased in the ACD group (OR 2.4; p = 0.026). The odds of asthma and food allergy in the ACD group were also increased; however, the difference was not statistically significant from the control group (OR 1.76 [p = 0.071] and OR 2.76 [p = 0.139], respectively). Conclusion: Patients with ACD had increased odds of eczema, allergic rhinitis, and atopic conditions overall. Asthma and food allergies were not found to have a statistically significant correlation. Larger studies that delve into atopic risk factors in ACD would be important to confirm these findings.

Fruit allergy and anaphylaxis in children: Culprit fruits and clinical findings.

Background: Fruit allergy usually presents with mild-to-moderate symptoms but serious systemic reactions, e.g., anaphylaxis, may also occur. Objective: This study aimed to examine the clinical and laboratory characteristics of patients with fruit allergy and fruit-induced anaphylaxis. Methods: Patients diagnosed with fruit allergy at Diskapi Hematology and Oncology Hospital and Bilkent City Hospital between January 2017 and January 2023 were included in the study. The diagnosis of anaphylaxis was made according to the European Allergy and Clinical Immunology Anaphylaxis Guideline. Results: During the study period, skin-prick tests with food allergens were performed on 9432 patients in our clinic, and fruit allergy was detected in 78 patients (0.82%). Five patients with inaccessible medical records were excluded from the study. 40 (54.8%) were boys. The median (interquartile range) age at the onset of symptoms was 72 months (12.5-144 months). Sixty-eight of the patients (93.2%) had a concomitant allergic disease, the most common of which was allergic rhinitis (n = 48 [65.8%]). The 73 patients had a history of reaction to 126 fruits. Twenty-five patients (19.8%) were allergic to multiple fruits. The most common fruit allergen was banana (22/126 [17.4%]), followed by peach (18/126 [14.2%]) and kiwi (17/126 [13.5%]). Mucocutaneous findings were observed most frequently after fruit consumption (120/126 [95.2%]). Anaphylaxis occurred in 17 patients (23.2%) with 21 fruits.The fruits most commonly associated with anaphylaxis were banana (6/21 [28.6%]) and kiwi (6/21 [28.6%]). Conclusion: Fruit allergy generally presents with mild symptoms, e.g., oral allergy syndrome, but severe systemic symptoms, e.g., anaphylaxis, can also be observed. Kiwi and banana are the fruits that most commonly cause anaphylaxis. Although more comprehensive studies are needed to comment on the development of tolerance, especially in patients with anaphylaxis, responsible fruit avoidance is still the most important strategy.

Effect of Symptom Levels of Children's Food Allergy on Maternal Depression: A Cross-sectional and Cohort Study.

BACKGROUND: Maternal depression may have negative impacts on children's behavior and mental health. Childhood food allergy is a common health issue, yet its relationship with maternal depression remains incompletely understood. This study aimed to analyze the association between children's food allergy symptoms and maternal depression through cross-sectional and cohort studies. METHODS: This study selected a total of 580 children with food allergy and their mothers who met the inclusion criteria in Ganzhou Women and Children's Health Care Hospital from April 2015 to April 2022, evaluated the symptom levels of children's food allergy according to the guidelines, assessed the depressive symptoms of mothers using self-rating depression scale (SDS), and analyzed the relationship between the symptom severity of children's food allergy and the risk of maternal depression; at the same time, one-year follow-up of mothers without depression was carried out to measure the incidence of depression to further explore this relationship. RESULTS: The 580 children with food allergies in the cross-sectional study consisted of 365 (62.93%) males and 215 (37.07%) females, aged (8.98 ± 2.30) years, with 298 (51.37%) experiencing Level-Ⅰ, and 282 (48.63%) experiencing Level-Ⅱ. A total of 56 (9.66%) mothers suffered from depression, aged (42.74 ± 5.42) years. Adjusting for confounders including mother's age, education level, marital status, family income, comorbidities, history of allergies, family history of food allergies, history of psychiatric disorders, current smoking status, current alcohol consumption, current regular exercise status, childhood food allergens and food allergy categorization, the mothers of children with child food allergy symptom Level-Ⅱ were found to have a higher risk of depression compared with mothers with child food allergy symptom Level-Ⅰ, odds ratio (OR) = 2.025 (95% confidence interval (CI): 1.319-3.128, p = 0.001). In the one-year cohort study, 38 (7.25%) mothers had new-onset depressive symptoms. Mothers of children with a child food allergy symptom Level-Ⅱ had an OR = 2.165 (95% CI: 1.612-2.902, p < 0.001) for depressive symptoms compared to mothers with a child food allergy symptom Level-Ⅰ. CONCLUSION: Among children with food allergy symptom scores of Level-Ⅰ and Level-Ⅱ, higher levels were associated with a higher prevalence of depression in their mothers.

Diagnosis and management of food allergy-induced constipation in young children-An EAACI position paper.

The recognition of constipation as a possible non-Immunoglobulin E (IgE)-mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE-mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non-IgE-Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review.

Assessing Feeding Difficulties in Children Presenting with Non-IgE-Mediated Gastrointestinal Food Allergies-A Commonly Reported Problem.

Many guidelines have been published to help diagnose food allergies, which have included feeding difficulties as a presenting symptom (particularly for non-IgE-mediated gastrointestinal allergies). This study aimed to investigate the prevalence of feeding difficulties in children with non-IgE-mediated gastrointestinal allergies and the association of such difficulties with symptoms and food elimination. An observational study was performed at Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Children aged 4 weeks to 16 years without non-allergic co-morbidities who improved on an elimination diet using a previously published Likert scale symptom score were included. This study recruited 131 children, and 114 (87%) parents completed the questionnaire on feeding difficulties. Feeding difficulties were present in 61 (53.5%) of the 114 children. The most common feeding difficulties were regular meal refusals (26.9%), extended mealtimes (26.7%), and problems with gagging on textured foods (26.5%). Most children (40/61) had ≥2 reported feeding difficulties, and eight had ≥4. Children with feeding difficulties had higher rates of constipation and vomiting: 60.7% (37/61) vs. 35.8% (19/53), p = 0.008 and 63.9% (39/61) vs. 41.5% (22/53), p = 0.017, respectively. Logistic regression analysis demonstrated an association between having feeding difficulties, the age of the child, and the initial symptom score. Gender and the number of foods excluded in the elimination diet were not significantly associated with feeding difficulties. This study found that feeding difficulties are common in children with non-IgE-mediated gastrointestinal allergies, but there is a paucity of food allergy specific tools for establishing feeding difficulties, which requires further research in the long-term and consensus in the short term amongst healthcare professions as to which tool is the best for food allergic children.

Alpha-gal syndrome: when treatment of hypovolemic shock can lead to anaphylaxis.

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature.

A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report.

This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.

Three cases of scombroid syndrome in Italy: clinical and preventive considerations.

Background: Foodborne diseases are common sources of morbidity and mortality worldwide. Scombroid syndrome represents a particular condition since it is not directly related to the ingestion of spoiled food but is determined by high levels of histamine, a chemical mediator naturally produced within the human body under particular conditions. In these cases, histamine is formed as a result of the bacterial activity from histidine, an amino acid present at high levels in some fish species. The resulting symptomatology can range from mild symptoms such as headache and skin rash to more severe manifestations such as hypotension and coronary spasms. Reference regulations in Italy set maximum levels of histamine in food at 200 mg/kg. Cases description: The cases described involve a family of three who, following the ingestion of a tuna dish, started to exhibit symptoms typical of an allergic reaction. In one case, hypotension, tachycardia, and electrocardiographic changes in the ST-tract suggestive of myocardial ischemia also appeared with negative myocardionecrosis enzyme dosage. All three cases experienced complete remission of symptoms in the absence of sequelae. Histamine concentrations in fish sampled three days later were 169 mg/kg. Conclusion: The cases described emphasize the importance of proper differential diagnosis as well as the importance of implementing specific controls in food hygiene.

COVID-19 and Asthma Onset in Children.

BACKGROUND AND OBJECTIVES: Respiratory viral infections increase risk of asthma in infants and children. Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause severe lung inflammation and prolonged respiratory symptoms. We sought to determine whether SARS-CoV-2 infection modified pediatric incident asthma risk. METHODS: This retrospective cohort study examined children ages 1 to 16 within the Children's Hospital of Philadelphia Care Network who received polymerase chain reaction (PCR) testing for SARS-CoV-2 between March 1, 2020 and February 28, 2021. Multivariable Cox regression models assessed the hazard ratio of new asthma diagnosis between SARS-CoV-2 PCR positive and SARS-CoV-2 PCR negative groups within an 18-month observation window. Models were adjusted for demographic characteristics, socioeconomic variables, and atopic comorbidities. RESULTS: There were 27 423 subjects included in the study. In adjusted analyses, SARS-CoV-2 PCR positivity had no significant effect on the hazard of new asthma diagnosis (hazard ratio [HR]: 0.96; P = .79). Black race (HR: 1.49; P = .004), food allergies (HR: 1.26; P = .025), and allergic rhinitis (HR: 2.30; P < .001) significantly increased the hazard of new asthma diagnosis. Preterm birth (HR: 1.48; P = .005) and BMI (HR: 1.13; P < .001) significantly increased the hazard of new asthma diagnosis for children <5 years old. CONCLUSIONS: SARS-CoV-2 PCR positivity was not associated with new asthma diagnosis in children within the observation period, although known risk factors for pediatric asthma were confirmed. This study informs the prognosis and care of children with a history of SARS-CoV-2 infection.

[Anaphylaxis due to legumes: case report]. / Anafilaxia por leguminosas: reporte de un caso.

BACKGROUND: Legumes belonging to the family Fabaceae of the order Fabales are a widely consumed source of protein. IgE-mediated hypersensitivity reactions to legumes have been described, the most studied allergens being peanuts and soybeans. In the Mediterranean region and India, lentils, chickpeas and peas have been considered important allergens and legumes have been reported to represent the fifth most common cause of food allergy in children under 5 years of age in Spain. In Latin America, there are few reports of allergy to legumes other than peanuts, and these are especially in the paediatric population. OBJECTIVE: To describe a case of IgE-mediated legume allergy in an adult female patient. CASE REPORT: We describe the case of a 65-year-old female patient who reports a 20-year history of generalized urticaria, accompanied by angioedema and dyspnea occurring immediately after consumption of lentils, beans, chickpeas, soya beans and cold meats, requiring admission to the emergency department for this cause. Tolerates peanuts. She does not report anaphylaxis in any context other than those described. He has presented generalized pruritus with exposure to fumes from cooking beans. Pathological history: Hypertension, type II diabetes mellitus, hypothyroidism. Allergic: Anaphylaxis due to penicillin at the age of 30. Other history: extensive local reaction to hymenoptera sting. Prick test trophoallergens: soya 3 mm. Prick to prick protein based on commercial soybean 7mm, chickpea 5mm, lentil 6mm and bean 7mm. He was negative for wheat and peanut (Image 1) (Attached in separate file). It has a normal tryptase report. Indication was given for adequate adrenaline and strict avoidance of legumes, except peanuts. CONCLUSIONS: Legume allergy is little known in our environment and mainly affects children. Clinical manifestations include mild reactions and anaphylaxis. A high degree of cross-reactivity among legumes has been reported. Lentils have cross-reactivity with chickpeas and beans. Peanut allergy may also be associated with allergy to lentils, chickpeas, and peas, but is less frequently reported.

ANTECEDENTES: Las leguminosas pertenecientes a la familia Fabaceae del orden Fabales, son una fuente de proteína de amplio consumo. Se han descrito reacciones de hipersensibilidad mediadas por IgE a las leguminosas, siendo los alérgenos más estudiados el maní y la soya. En la región mediterránea y en India, las lentejas, garbanzos y arvejas se han considerado alérgenos importantes, y se ha informado que las leguminosas representan la quinta causa más común de alergia alimentaria en niños menores de cinco años en España. En América Latina, hay pocos reportes de alergia a las leguminosas diferentes al maní, y éstos son, especialmente, en población pediátrica. OBJETIVO: Describir el caso de alergia mediada por IgE a leguminosas, en una paciente adulta. REPORTE DE CASO: Se describe el caso de una paciente de 65 años, quien reporta un cuadro de 20 años con evolución consistente de urticaria generalizada, acompañada de angioedema y disnea, que ocurre, en forma inmediata, tras el consumo lentejas, fríjoles, garbanzos, soya y carnes frías; y requiere de ingresos al servicio de urgencias por esta causa. Tolera maní. No se reporta anafilaxia en otro contexto diferente a los descritos. Ha presentado prurito generalizado con la exposición a vapores de la cocción de fríjoles. Antecedentes patológicos: hipertensión arterial, diabetes mellitus tipo II, hipotiroidismo. Alérgicos: Anafilaxia por Penicilina a los 30 años. Otros antecedentes: Reacción local extensa con picadura de himenópteros. Prick test trofoalérgenos: soya 3 mm. Prick to prick proteína a base de soya comercial 7mm, garbanzo 5mm, lenteja 6mm y fríjol 7mm. Fue negativa para trigo y maní (Imagen 1). (Adjunta en archivo separado). Tiene reporte de triptasa normal. Se dio indicación de porte adecuado de adrenalina y evitación estricta de leguminosas, excepto maní. CONCLUSIONES: La alergia a las leguminosas es poco conocida en nuestro medio, y afecta principalmente a los niños. Sus manifestaciones clínicas incluyen reacciones leves y anafilaxia. Se ha informado, un alto grado de reactividad cruzada entre las leguminosas. Las lentejas tienen reactividad cruzada con garbanzos y fríjoles. La alergia al maní también puede estar asociada con la alergia a lentejas, garbanzos y guisantes, pero se informa con menos frecuencia.

Are children with food allergies more likely to have lower urinary tract symptoms? A case-control study.

INTRODUCTION: There are multiple historic reports linking lower urinary tract symptoms (LUTS) in children with food allergies (FA), but contemporary studies are sparse. The objective of this study was to evaluate a potential link between FA and LUTS in the pediatric population. We hypothesized that children with FAs are more likely to have LUTS. MATERIALS AND METHODS: After local IRB approval, pediatric patients (6-17 years [y]) with FAs proven by positive skin prick and/or serum IgE testing were invited to participate. A control group of pediatric patients without FAs was also recruited. All families/legal guardians signed informed consent, and all children signed written assent. Each participant filled out the Vancouver Symptom Score (VSS), a validated questionnaire for dysfunctional elimination syndrome, and the Pediatric Incontinence Questionnaire (PinQ), a validated quality of life assessment for children with bladder dysfunction. Demographic and clinical information were obtained retrospectively. RESULTS: From 2019-2020, 26 children with FAs and 57 without agreed to participate. Mean age was 9.3 y (IQR 7.9 y-13.5 y). There were no differences in gender, age, or race between the two cohorts. There were no significant differences between the two groups in mean VSS score or mean PinQ score. Four children with FAs (15%) and 15 children without (26%) had VSS score ≥ 11 (p = 0.339), indicating dysfunctional elimination. The median PinQ score was 0 (IQR 0-2) in both cohorts. CONCLUSIONS: This study did not identify an association between FAs and LUTS in a population of pediatric patients with laboratory proven FAs.

Early childhood neurodevelopmental milestones in children with allergic diseases: the Japan Environment and Children's Study (JECS).

This study investigated the potential link between early childhood allergic diseases and neurodevelopmental milestone attainment during the first 3 years of life. Utilizing data from a large-scale prospective birth cohort study in Japan, encompassing 87,986 children, we examined physician-diagnosed and caregiver-reported allergic conditions, including atopic dermatitis (AD), asthma, and food allergy (FA). Neurodevelopmental milestones were assessed using the Ages and Stages Questionnaires at 1, 1.5, 2, 2.5, and 3 years of age. Stabilized inverse probability-weighted generalized estimating equation models were employed to estimate odds ratios (ORs). Our analysis revealed no significant association of AD and asthma with delay in communication, gross motor, fine motor, problem-solving, and personal-social skills during the initial 3 years of life. However, children with FA showed an increased likelihood of experiencing gross motor delay compared with that shown by those without FA (weighted adjusted OR: 1.14). Despite this, no significant association of FA with other developmental domains was observed. Early childhood allergies may not influence neurodevelopmental delays. However, there is a potential association between FA and delays, specifically in gross motor skills, that warrants routine developmental monitoring and additional investigations.

Management of Food Allergies and Food-Related Anaphylaxis.

Importance: An estimated 7.6% of children and 10.8% of adults have IgE-mediated food-protein allergies in the US. IgE-mediated food allergies may cause anaphylaxis and death. A delayed, IgE-mediated allergic response to the food-carbohydrate galactose-α-1,3-galactose (alpha-gal) in mammalian meat affects an estimated 96 000 to 450 000 individuals in the US and is currently a leading cause of food-related anaphylaxis in adults. Observations: In the US, 9 foods account for more than 90% of IgE-mediated food allergies-crustacean shellfish, dairy, peanut, tree nuts, fin fish, egg, wheat, soy, and sesame. Peanut is the leading food-related cause of fatal and near-fatal anaphylaxis in the US, followed by tree nuts and shellfish. The fatality rate from anaphylaxis due to food in the US is estimated to be 0.04 per million per year. Alpha-gal syndrome, which is associated with tick bites, is a rising cause of IgE-mediated food anaphylaxis. The seroprevalence of sensitization to alpha-gal ranges from 20% to 31% in the southeastern US. Self-injectable epinephrine is the first-line treatment for food-related anaphylaxis. The cornerstone of IgE-food allergy management is avoidance of the culprit food allergen. There are emerging immunotherapies to desensitize to one or more foods, with one current US Food and Drug Administration-approved oral immunotherapy product for treatment of peanut allergy. Conclusions and Relevance: IgE-mediated food allergies, including delayed IgE-mediated allergic responses to red meat in alpha-gal syndrome, are common in the US, and may cause anaphylaxis and rarely, death. IgE-mediated anaphylaxis to food requires prompt treatment with epinephrine injection. Both food-protein allergy and alpha-gal syndrome management require avoiding allergenic foods, whereas alpha-gal syndrome also requires avoiding tick bites.

A nomogram for predicting food allergy in infants with feeding problems and malnutrition.

BACKGROUND AND OBJECTIVE: As oral food challenge (OFC) cannot be performed routinely in the general outpatient, this study aimed to construct a nomogram to predict the odds of food allergy in infants with idiopathic feeding problems and malnutrition. METHODS: From August 2018 to December 2021, 289 infants (median age, 6 months; P25-P75, 4-8) with idiopathic feeding problems and malnutrition were enrolled from seven hospitals in Shanghai, China. Food allergy was defined as a positive response to a skin prick test or OFC, with gastrointestinal, dermatologic, or respiratory symptom improvement after 4 weeks of avoidance of the suspected food. Demographic characteristics, Cow's Milk-related Symptom Scores (CoMiSS), and blood eosinophil amounts were evaluated for their associations with food allergy. Multivariable logistic regression analysis was used to identify variables to develop a nomogram model with the bootstrapped-concordance index as an assessment metric. RESULTS: Totally 249 of 289 infants had food allergy (86.2%). After logistic regression analysis, the feeding pattern (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 2.13-13.09), a family history of allergy (OR = 1.79, 95% CI: 0.71-4.51), CoMiSS (OR = 1.45, 95% CI: 1.19-1.77), and eosinophil percentage (OR = 1.33, 95% CI: 1.11-1.60) were used to develop the model, which had a good performance with an area under the curve of 0.868 (95% CI: 0.792-0.944) and a bootstrapped-concordance index of 0.868. CONCLUSION: Food allergy is common in infants with idiopathic feeding problems and malnutrition. The developed nomogram may help identify infants with food allergy for further diagnosis.

Outcomes of Serum Food-Specific Immunoglobulin G 4 to Guide Elimination Diet in Patients With Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes. METHODS: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up. RESULTS: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up. DISCUSSION: Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.

A randomized, double-blind placebo-controlled study on the efficacy of Omalizumab on food allergy threshold in children with severe food allergy.

BACKGROUND: Food allergy is common in childhood with some children having a low threshold and being difficult to protect from accidental ingestion of the offending food. Therapies for this potentially life-threatening condition are highly needed. The aim of this study was to evaluate the efficacy of Omalizumab in food-allergic children. METHODS: This is a single-center, double-blind, placebo-controlled study. Food allergic children with a cumulative threshold ≤443 mg food protein at DBPCFC were randomized to Omalizumab (asthma dose) or placebo (3:1). After 3 months, a second DBPCFC was performed (steps 3, 10, 30, 100, 300, 1000, and 3000 mg food protein), followed by a separate open challenge up to 10,000 and 30,000 mg food protein if negative. Responders were defined as ≥2-step increases in threshold. Non-responders received high-dose Omalizumab. A third DBPCFC was performed after 6 months. Skin testing, blood samples, and the severity of atopic co-morbidity were registered during the study and 3 months after treatment. RESULTS: In total, 20 children were evaluated at 3 months (14 Omalizumab, 6 placebo). All treated with Omalizumab increased their threshold at least two steps and with a significant difference between the Omalizumab and the placebo group (p = .003), although the intended number of included children was not reached. The threshold before Omalizumab treatment was 13-443 mg food protein while the threshold after 3 months of treatment increased up to 44,000 mg (1143-44,000). In the placebo group, two children improved threshold during the study. CONCLUSION: An increase in the threshold level during Omalizumab treatment significantly improve patient safety and protected all children against small amount of allergen.

Food protein-induced allergic proctocolitis in infants is associated with low serum levels of macrophage inflammatory protein-3a.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is a nonimmunoglobulin (IgE)-mediated food hypersensitivity and the exact mechanisms that cause FPIAP are unknown. Chemokines play crucial roles in the development of allergic diseases. OBJECTIVE: To examine serum levels of a group of chemokines in infants with FPIAP. METHODS: In 67 infants with FPIAP and 65 healthy infants, we measured serum levels of mucosa-associated epithelial chemokine (MEC/CCL28), thymus-expressed chemokine (TECK/CCL25), CX3CL1 and macrophage inflammatory protein (MIP)-3a/CCL20. RESULTS: Infants with FPIAP had a lower median value of MIP3a/CCL20 than healthy infants [0.7 (0-222) vs. 4 (0-249) pg/mL, respectively] (p < 0.001). Infants with MIP3a/CCL20 levels ≤0.95 pg/mL have 13.93 times more risk of developing FPIAP than infants with MIP3a/CCL20 levels >0.95 pg/mL. Serum MEC/CCL28, TECK/CCL25, and CX3CL1 levels were similar between the infants with FPIAP and the control group. CONCLUSION: MIP3a/CCL20 serum levels were reduced in infants with FPIAP compared with healthy controls. Whether this finding has a role in pathogenesis remains to be determined.

Progressive accumulation of hyperinflammatory NKG2Dlow NK cells in early childhood severe atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic comorbidities remain ill-defined. Here, analysis of circulating NK cells in a longitudinal early life cohort of children with AD revealed a progressive accumulation of NK cells with low expression of the activating receptor NKG2D, which was linked to more severe AD and sensitivity to allergens. This was most notable in children co-sensitized to food and aeroallergens, a risk factor for development of asthma. Individual-level longitudinal analysis in a subset of children revealed coincident reduction of NKG2D on NK cells with acquired or persistent sensitization, and this was associated with impaired skin barrier function assessed by transepidermal water loss. Low expression of NKG2D on NK cells was paradoxically associated with depressed cytolytic function but exaggerated release of the proinflammatory cytokine tumor necrosis factor-α. These observations provide important insights into a potential mechanism underlying the development of allergic comorbidity in early life in children with AD, which involves altered NK cell functional responses, and define an endotype of severe AD.