Advancements in Anaphylaxis Management.

Anaphylaxis is defined as a severe life-threatening, generalized or systemic hypersensitivity reaction. Yet, anaphylaxis is often difficult to diagnose, leading to a delay in applying appropriate management. Epinephrine is the medication of choice for the immediate treatment of anaphylaxis. The rest of the actions to be taken during the acute anaphylaxis episode, including administering other medications, will depend on the response to epinephrine. Epinephrine auto-injectors (EAI) are the preferred method for administering the treatment of anaphylaxis in the community setting. However, there are multiple potential barriers to using epinephrine during an anaphylactic reaction related to the physicians and the patients themselves. Strategies to overcome gaps in the acute management of anaphylaxis include novel injection devices and research of new routes for epinephrine delivery. Electronic health solutions may also have a role at this level. Long-term management of anaphylaxis is focused on the prevention of new episodes. Etiologic diagnosis and patient education are key to this end. The application of health information technologies, such as telemedicine, social media, and mobile health, can be helpful for the long-term management of anaphylaxis. Additionally, some patients may benefit from long-term immunomodulatory and etiologic treatments when allergen avoidance implies negative consequences. This review article addresses the most recent advances regarding the integral management of anaphylaxis, including pharmacological and non-pharmacological measures.

Oral Immunotherapy and Risk of Eosinophilic Esophagitis in Children: 15 Years' Experience.

OBJECTIVES: Oral immunotherapy (OIT) is an effective treatment for children with persistent food allergy, and has concerns about its safety, including eosinophilic esophagitis (EoE). The aim of this study was to evaluate the prevalence of EoE in a large cohort of children who underwent OIT in our center, and to determine if there were any clinical, endoscopic, or histologic differences depending on the food employed for the OIT. METHODS: A retrospective study was performed over a 15-year period (2005-2020). Children who underwent cow's milk (CM), egg, and/or peanut OIT and developed EoE were included. RESULTS: Six hundred and seven OIT were carried out (277 CM-OIT, 322 egg-OIT, and 8 peanut-OIT). Seventeen patients (2.8%) had a confirmed histologic diagnosis of EoE with a higher prevalence for patients who underwent CM-OIT (3.9%) than egg-OIT (2.2%). Symptoms suggestive of EoE and a confirmed diagnosis occurred at median times of 25 and 36 months, respectively, after the build-up phase of the OIT was completed. Choking, abdominal pain, and dysphagia were the most frequent symptoms and lamina propria fibrosis was observed in 41.2% of patients. No significant differences in clinical symptoms, endoscopic, or histologic findings between patients under CM or egg-OIT were found. One-third of patients reported mild symptoms suggestive of EoE before the OIT. CONCLUSIONS: EoE appears to be a rare but important adverse event that can occur even years after OIT. Validated questionnaires to screen EoE before the OIT and in the follow-up of these patients may be the main tool for an early diagnosis.

An unusual case of food protein-induced enterocolitis syndrome due to zucchini.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by gastrointestinal symptoms, mainly protracted and delayed vomiting. Diagnosis is based on clinical history, and it can be challenging as symptoms are delayed and the causative food is often not very suspicious. OBJECTIVE: This case report highlights the importance of having a high degree of suspicion to reach a correct diagnosis. MATERIALS AND METHODS: We report an unusual case of FPIES due to zucchini. During the follow-up. Two oral food challenges (OFC) were carried out to evaluate tolerance to the food involved. RESULTS: The first OFC was positive and in the second the child tolerated the food without problems. CONCLUSIONS: In this case, the OFC was essential to identify the offending food and to verify that the child had overcome the disease.

Poor prognosis of food protein-induced enterocolitis syndrome to fish.

BACKGROUND: Fish is the most common causative food of food protein-induced enterocolitis syndrome (FPIES) in Southern Europe. In children with FPIES, the development of tolerance varies according to the culprit food and specifically fish seems to have a poorer prognosis than other solid foods. We sought to evaluate the fish-FPIES resolution rate in children. METHODS: A descriptive retrospective analysis of children with fish-FPIES, followed during the last 20 years, was performed. The offending fish, age and symptoms at onset, the coexistence of atopic diseases and FPIES to other foods were registered. All the children included had undergone an oral food challenge (OFC) with the offending fish. We recorded those children that overcame their fish-FPIES and those that did not outgrow the disease. RESULTS: Seventy children were enrolled in this study (median age: 9 yo; IQR 6.4-13.8). Forty-two (60%) achieved tolerance to the offending fish with a median age of 4 years (IQR: 3-5). Among children ≤5 yo (n = 40), 35 (87.5%) developed tolerance; among 6-8yo (n = 14), 40% developed tolerance; and only 12.5% among those ≥9 yo (n = 16) developed tolerance. Twenty-eight children did not outgrow the disease (median age: 8.9 yo; IQR: 9-13.8). We did not find any statistical differences regarding the offending fish, presence of single vs multiple fish-FPIES, symptoms at the beginning, coexistence of other atopic diseases or the coexistence of other FPIES, between the children who overcame the disease and those who did not. CONCLUSION: One in five children with FPIES to fish will not overcome the disease during childhood.

Oral Food Challenge in Food Protein-Induced Enterocolitis Syndrome by Fish: Is There Any Room for Improvement?

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity usually due to cow's milk or soy. Among the solid foods, rice is one of the most causative foods worldwide, but it varies depending on the geographic area. In the Mediterranean countries, fish is one of the most important triggers of FPIES. There is not a specific biological marker for the disease that allows us to confirm the diagnosis or to predict when tolerance to the offending food has been achieved, so all patients with a FPIES diagnosis undergo an oral food challenge (OFC) at least once. The OFC is a risky procedure and many patients develop severe symptoms. OBJECTIVE: We sought to evaluate the safety of a new OFC protocol in children with fish-FPIES. METHODS: A retrospective study was performed over a 22-year period (1996-2018). We compared two methodologies used in the OFC: Method 1 that consisted in giving several doses during the same day versus Method 2 that consisted in giving a unique dose per day on 2 or three non-consecutive days. RESULTS: A total of 75 positive OFC with fish done in 40 children were included. Forty-three (57.3%) OFC were performed following Method 1 and 32 (42.7%) with Method 2.The severity of the symptoms of the OFC done with Method 1 was mostly moderate (41.9%) followed by severe (39.5%) and mild (18.6%). The adverse reactions with Method 2 were mostly mild (68.8%) and only 18.8 and 12.5% presented moderate or severe symptoms, respectively. CONCLUSIONS: OFC performed in children with fish-FPIES are risky and many patients develop moderate or severe symptoms after this procedure. We propose a new protocol that has demonstrated to improve safety.

Peanut Allergy in Spanish Children: Comparative Profile of Peanut Allergy versus Tolerance.

BACKGROUND: Peanut storage proteins (Ara h 1, Ara h 2, and Ara h 3) have been described as the major peanut allergens in children, although not all peanut-sensitized individuals have clinical reactivity after exposure. OBJECTIVES: We studied the sensitization profile of peanut-allergic and peanut-tolerant children in a pediatric cohort. METHODS: The clinical features and sensitization profile to the peanut storage proteins Ara h 9 and Pru p 3 were compared between peanut-allergic and peanut-tolerant children using component-resolved diagnostics. RESULTS: Thirty-three peanut-sensitized children were included: 22 allergic and 11 tolerant patients. Seventy-two percent of the peanut-allergic children were sensitized to at least one peanut storage protein. The rates of sensitization to Ara h 1, Ara h 2, and Ara h 3 were 63.6, 68.1, and 68.1%, respectively, among the peanut-allergic children and 27.2, 18.1, and 45.4% among the peanut-tolerant children. IgE from the sera of 18% of the peanut-allergic patients recognized Ara h 9, whereas no sensitization to Ara h 9 was detected in the peanut-tolerant children. A total of 59% of the peanut-allergic and 27% of the peanut-tolerant children were sensitized to Pru p 3. Sensitization to Ara h 1 and Ara h 2 was more frequent among the peanut-allergic children (p < 0.05). Although the levels of specific IgE against peanut storage proteins were higher in peanut allergy, there were not statistically significantly different from the levels in peanut tolerance, probably due to the small number of patients included. CONCLUSIONS: In our population, the peanut-allergic children were mainly sensitized to peanut storage proteins, and Ara h 2 sensitization allows a more accurate diagnosis of clinical reactivity to peanuts. More than half of the peanut-allergic patients were sensitized to peach Pru p 3, and 50% of them had fruit allergy at the time of the study.

Egg oral immunotherapy in children (SEICAP I): Daily or weekly desensitization pattern.

BACKGROUND: Studies are required before incorporating egg oral immunotherapy (OIT) into clinical practice. The Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology (SEICAP) conducted a multicenter, randomized controlled study assessing the effectiveness and safety of the OIT using pasteurized egg white (PEW) in egg-allergic children. METHODS: One hundred and one egg-allergic children (6-9 years) were randomized for 1 year: 25 to an egg-free-diet (CG) and 76 to OIT (target dose 3.3 g PEW proteins), PI (30% weekly plus 5% daily increments) or PII (only 30% weekly increments) buildup patterns. Egg skin prick test, sIgE and sIgG4 serum levels, PEW double-blind placebo-controlled food challenge (DBPCFC), and dosing adverse reactions (DARs) were evaluated in all patients from inclusion (T0) until completing 1 year of follow-up (T12). At T12, egg-allergic control patients could start OIT. The effectiveness and safety of OIT and the effect of the buildup pattern were analyzed. RESULTS: At T12, 4/25 (16.0%) CG patients passed the PEW DBPCFC vs 64/76 (84.2%) OIT that reached total desensitization (P = 0.000); 12 egg-allergic control patients started OIT. Finally, 72/88 (81.81%) patients reached total desensitization, 96.15% PI vs 75.80% on PII (P = 0.01). Induction period (121.12 ± 91.43, median 98.00 days) was longer in patients on PII buildup pattern, and those with allergic asthma, minor threshold dose, or higher egg sIgE (P < 0.05). Most patients (89.06%) developed DARs: 74.53% were mild; 21.90% moderate; and 3.5% requiring adrenaline-treatment. Moderate reactions and those requiring adrenaline were more frequent in patients with allergic asthma, PII pattern, or higher egg sIgE serum antibody levels (P < 0.05). CONCLUSIONS: PEW OIT is an effective treatment for children with persistent egg allergy. A 30% weekly plus 5% daily increment pattern could be more effective and safer than one with only 30% weekly increments.

Egg OIT in clinical practice (SEICAP II): Maintenance patterns and desensitization state after normalizing the diet.

BACKGROUND: It is unknown which are the most suitable maintenance pattern and egg consumption to maintain the desensitization state after ending the oral immunotherapy (OIT). This multicenter, randomized, controlled trial compared two OIT maintenance patterns with pasteurized egg white (PEW), evaluating the egg consumption effect on the desensitization state after ending the OIT. METHODS: One hundred and one children with confirmed egg allergy were randomized: 25 to an egg-free diet (CG) and 76 to an OIT year with PEW and two maintenance patterns, 38 patients to daily 3.3 g proteins (AG) and 38 to every two days (BG). PEW challenge (DBPCFC), adverse reactions, and immune markers were assessed at baseline, at the end of the OIT, and at 6 and 12 months later on ad libitum egg consumption (T0, T12, T18, and T24). A questionnaire evaluated the egg consumption at T18. RESULTS: At T12, 64 of 76 (84.21%) OIT patients had reached total desensitization (32 AG and 32 BG) vs 4 of 25 (16.00%) CG who passed the PEW DBPCFC. Thirty (93.75%) AG vs 25 (78.12%) BG patients completed an OIT year. At T18, 27 of 29 (93.1%) AG vs 20 of 24 (83.3%) BG passed the PEW DBPCFC, 96% consuming at least two egg servings/week. At T24, 97.43% OIT patients passed the challenge. Most patients had adverse reactions, more frequent in the BG patients; frequency and severity of reactions decreased through the study. PEW skin prick test wheal and sIgE antibody serum levels similarly decreased in AG or BG, but AG patients had greater increase in PEW sIgG4 (P < 0.05). CONCLUSIONS: Daily OIT maintenance achieves better adherence, effectiveness, and safety. Two egg servings/week ensure maintained desensitization after the end of an OIT year.

Celiac Disease and Wheat Allergy: A Growing Association?

INTRODUCTION: Celiac disease and wheat allergy (WA) are infrequent diseases in the general population, and a combination of the 2 is particularly rare. Celiac disease occurs in around 1% of the general population and WA in around 1% of all children. CASE REPORT: We report 2 patients with celiac disease and a gluten-free diet who developed WA consistent in anaphylaxis and an eyelid angioedema, respectively, through accidental wheat exposure. A serum study and an intestinal biopsy confirmed celiac disease. Both patients were studied with a skin prick test and serum-specific IgE, with a diagnosis of WA. DISCUSSION: In patients with celiac disease, the trace amounts of cereals present in gluten-free food could act as a sensitization factor, and probably patients with persistent symptoms (despite a gluten-free diet) are experiencing WA symptoms rather than celiac disease symptoms. The number of patients diagnosed with celiac disease has increased in the recent decades: the association between celiac disease and WA, exceedingly rare to date, could increase as well, prompting special attention to the possibility of inadvertent intake of cereals.

Oral immunotherapy in hen's egg-allergic children increases a hypo-proliferative subset of CD4+ T cells that could constitute a marker of tolerance achievement.

BACKGROUND: Food allergy affects a significant number of children and its prevalence, and persistence is undergoing an important increase in the last years. Specific oral tolerance induction (SOTI) is a promising therapy for food allergy. However, little is known about the immune mechanisms implicated in the desensitization to allergens. Our purpose was to study which immune parameters are modified during the process of tolerance achievement with the goal of identifying markers of tolerance induction. METHODS: We performed an extensive immune analysis in 19 allergic children following SOTI with hen's egg before and after the immunotherapy. Changes in lymphocyte subpopulations and serum cytokines were identified in children with desensitization achievement. RESULTS: Sixteen children achieved complete tolerance to egg, and the immune analysis reveals that desensitization was accompanied in all the cases by a significant decrease in the percentage and absolute counts of effector-memory CD4+ T cells (T(EM) ) and a marked increase in the absolute counts of a subset of CD4(+) CD38(+) CD45RO(-) cells. Additionally, we also observed a marked reduction in the plasma levels of different Th1 and Th2 cytokines after tolerance achievement. CONCLUSIONS: Acquisition of tolerance in children after oral immunotherapy is accompanied by a decrease in the T(EM) population and the increase in a particular subset of CD4+ T cells with a hypo-proliferative and non-reactive phenotype. This hypo-proliferative subset of cells could constitute a marker of the development of oral tolerance, and the study of this subset could contribute to the better understanding of the immune responses in allergic subjects.

Allergy to pine processionary caterpillar (Thaumetopoea pityocampa) in children.

UNLABELLED: Contact with pine processionary caterpillar (Thaumetopoea pityocampa) induces dermatitis usually located in exposed areas through a toxic-irritative mechanism. Over the last few years an immediate hypersensitivity mechanism have mainly been demonstrated in adult patients. However, there are few studies carried out in children. OBJECTIVE: To evaluate a group of 16 children who experienced allergic reactions after exposure to pine processionary caterpillar. PATIENTS AND METHODS: All patients underwent allergy testing through skin prick test. Serum specific IgE determination was performed by EAST technique. The molecular mass of the IgE -binding bands was studied by SDS-PAGE Immunoblotting. RESULTS: Skin prick test with the caterpillar extract was positive in all patients. Specific IgE was positive (higher than 0.35 kU/L) in 15 patients' sera. Western blotting showed several IgE-binding bands with molecular mass values ranging from 17.5 to 168 kDa. Electrophoretic mobility of some of the relevant allergens was related to the conditions of sample preparation (reduced or non-reduced). CONCLUSIONS: The results of this study demonstrate the existence of an allergic IgE-mediated mechanism caused by pine processionary caterpillar proteins. Airborne urticating hairs of this animal should be considered as seasonal inhalant allergen, which is able to induce allergic pathologies in children who frequent pine areas.

Allergy to pine processionary caterpillar (Thaumetopoea pityocampa) in children / Alergia a la procesionaria del pino (thaumetopoea pityocampa) en niños

Contact with pine processionary caterpillar (Thaumetopoea pityocampa) induces dermatitis usually located in exposed areas through a toxic-irritative mechanism. Over the last few years an immediate hypersensitivity mechanism have mainly been demonstrated in adult patients. However, there are few studies carried out in children. Objective: To evaluate a group of 16 children who experienced allergic reactions after exposure to pine processionary caterpillar. Patients and methods: All patients underwent allergy testing through skin prick test. Serum specific IgE determination was performed by EAST technique. The molecular mass of the IgE ­binding bands was studied by SDS-PAGE Immunoblotting. Results: Skin prick test with the caterpillar extract was positive in all patients. Specific IgE was positive (higher than 0.35 kU/L) in 15 patients' sera. Western blotting showed several IgE-binding bands with molecular mass values ranging from 17.5 to 168 kDa. Electrophoretic mobility of some of the relevant allergens was related to the conditions of sample preparation (reduced or non-reduced). Conclusions: The results of this study demonstrate the existence of an allergic IgE-mediated mechanism caused by pine processionary caterpillar proteins. Airborne urticating hairs of this animal should be considered as seasonal inhalant allergen, which is able to induce allergic pathologies in children who frequent pine areas

El contacto con la procesionaria del pino (Thaumetopoea pityocampa) produce diversos cuadros cutáneos, localizados, principalmente, en zonas expuestas, mediante un mecanismo tóxixo-irritativo. En los últimos años se ha demostrado un mecanismo de hipersensibilidad inmediata en pacientes generalmente adultos. Sin embargo, los estudios realizados en niños son escasos. Objetivo: Estudiar 16 casos de niños que sufrieron reacciones alérgicas tras exposición a procesionaria del pino. Material y métodos: En todos los pacientes se realizó estudio alergológico mediante pruebas cutáneas en prick y detección de IgE específica en el suero. Se estudió la masa molecular de las proteínas fijadoras de IgE específica mediante la técnica de SDS-PAGE Immunoblotting. Resultados: Las pruebas cutáneas con el extracto de procesionaria del pino fueron positivas en todos los pacientes. La detección de IgE específica fue positiva ( > 0,35 kU/L) en 15 pacientes. En el Immunoblotting se detectaron varias bandas fijadoras de IgE, con masas moleculares comprendidas entre 17.5 y 168 kDa. La movilidad electroforética de algunos de los alérgenos relevantes se modifica por la presencia de un agente reductor (β-mercaptoetanol). Conclusión: Los resultados de este estudio muestran un mecanismo alérgico de hipersensibilidad mediado por IgE en estas reacciones. Las espículas urticantes aerotransportadas de la procesionaria del pino deberían considerarse como potenciales neumoalérgenos estacionales, capaces de desencadenar patologías alérgicas en niños que frecuenten zonas próximas a pinares