Analysis of the characteristics of intestinal microbiota after oral tolerance in infants with food protein-induced proctocolitis.

Objective: To understand the characteristics of the intestinal microbiota after oral tolerance in infants with food protein-induced proctocolitis (FPIAP) treated with amino acid formula and their differences from healthy children, aiming to provide a scientific basis for guiding the application of probiotics during treatment. Methods: FPIAP infants were prospectively enrolled, fecal specimens were obtained, and DNA was extracted for PCR amplification of the bacterial 16S rRNA gene V4 region. Library construction and sequencing were performed, and bioinformatic analysis was performed after obtaining valid data. Results: There were 36 patients in the FPIAP group: 20 males and 16 females, age 21.944 ± 13.277 months. Diarrhea with blood in the stool were the main symptom, with an average course of 14.83 ± 9.33 days. Thirty infants (83.33%) had mucus stool, 11.11% (4/36) of them experiencing vomiting, and 55.56% (20/36) of the infants displaying poor intake and weight gain, 28 (77.78%) patients with moderate eczema, 2 (5.6%) patients with chronic respiratory symptoms. The treatment time with amino acid formula was 5.51 ± 2.88 months. A control group comprising of 25 healthy infants who were full-term, natural delivery, bottle fed, and matched in terms of age (24.840 ± 12.680 months) and gender (15 males and 10 females) was selected. Anaerobic bacteria were less abundant in FPIAP infants than healthy infants (P = 4.811 × 10-5), but potentially pathogenic bacteria were more abundant (P = 0.000). The abundance of Actinobacteria was low in FPIAP infants, the abundance of Proteobacteria was high, and the abundance of Firmicutes was reduced. Bifidobacterium could be used as a bacterial genus to differentiate healthy and FPIAP infants. Both α-and ß-diversity indicators of intestinal microbiota were lower in FPIAP infants. In FPIAP infants, glucose and energy metabolism and amino acid anabolism were decreased, and inflammation-related lipopolysaccharide synthesis pathways were increased. Conclusion: Compared with healthy infants, FPIAP infants with oral tolerance after amino acid formula treatment had differences in the structure and diversity of intestinal microbiota, among which Bifidobacterium was significantly reduced. Trial Registration: This trial was registered on https://register.clinicaltrials.gov/.

To Diet or Not to Diet This Is the Question in Food-Protein-Induced Allergic Proctocolitis (FPIAP)-A Comprehensive Review of Current Recommendations.

Food-protein-induced allergic proctocolitis (FPIAP) is an increasingly reported transient and benign form of colitis that occurs commonly in the first weeks of life in healthy breastfed or formula-fed infants. Distal colon mucosal inflammation is caused by a non-IgE immune reaction to food allergens, more commonly to cow's milk protein. Rectal bleeding possibly associated with mucus and loose stools is the clinical hallmark of FPIAP. To date, no specific biomarker is available, and investigations are reserved for severe cases. Disappearance of blood in the stool may occur within days or weeks from starting the maternal or infant elimination diet, and tolerance to the food allergen is typically acquired before one year of life in most patients. In some infants, no relapse of bleeding occurs when the presumed offending food is reassumed after a few weeks of the elimination diet. Many guidelines and expert consensus on cow's milk allergy have recently been published. However, the role of diet is still debated, and recommendations on the appropriateness and duration of allergen elimination in FPIAP are heterogeneous. This review summarizes and compares the different proposed nutritional management of infants suffering from FPIAP, highlighting the pros and cons according to the most recent literature data.

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.

A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

BACKGROUND: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. METHODS: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). RESULTS: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about "diagnosis-probable" patient cohort (n = 402) and the "diagnosis-confirmed" patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. CONCLUSIONS: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

Cow's Milk Protein Allergy.

Cow's milk allergy refers to an immunological reaction to milk protein. It is one of the commonest food protein allergies with an estimated prevalence of 0.5% to 3% at 1 y of life. The disease may be IgE or non-IgE mediated or mixed with a wide range of symptoms often involving multiple organ systems. Gastrointestinal manifestations are common in non-IgE disease and may consist of enteropathy, proctocolitis, colic, reflux-like symptoms, constipation, enterocolitis syndrome and eosinophilic esophagitis. The gold standard for diagnosis remains a double-blind placebo-controlled oral challenge. Specific IgE and skin prick tests may predict severe and persistent disease, and aid in deciding on reintroduction or oral immunotherapy; however, they do not contribute to a definitive diagnosis as they indicate only sensitization. In practice, an elimination diet followed by open challenge under medical supervision is often used for diagnosis except when symptoms are severe such as anaphylaxis. Management consists of the elimination of the allergen with resolution of symptoms between 1-4 wk later depending on the type of allergy. Extensively hydrolyzed and Amino acid formulas are used to substitute milk in infants. Soy-based formulas are often utilized in resource-limited settings. Tolerance to the protein develops over time and periodic reintroduction should be attempted every six months after the initial one year of elimination diet. Oral immunotherapy is a newer treatment technique for IgE-mediated disease. There is no firm evidence on prevention apart from recommending breast feeding in early life along with initiating complementary feeding between 4-6 mo age.

What is Known About Cow's Milk Protein Allergy in Preterm Infants?

Background: Cow's milk protein allergy (CMPA) is well described in term infants, as opposed to preterm infants. In preterm infants, CMPA shares many gastrointestinal symptoms with necrotizing enterocolitis (NEC). Objectives: To evaluate the presentation of CMPA in preterm infants and to investigate the different diagnostic and therapeutic options. Materials and Methods: We searched for the relevant literature using the medical databases PubMed, Web of Science, and the Cochrane Library. We performed a post hoc analysis on the 25 case reports included in this study. Results: Literature was scarce and heterogeneous. The majority of preterm infants with CMPA were exposed to bovine-based milk proteins before the development of symptoms. The most common clinical manifestations were bloody stools, vomiting, and abdominal distension. Of the 25 cases, only 7 (28%) retained human milk in their diet after diagnosis. In the larger studies, no study has human milk as primary feeding choice after diagnosis. Conclusions: Preterm infants exposed to a type of cow's milk-based formula in their first days of life have a higher risk of developing CMPA. Most of the preterm infants are no longer fed with human milk after the diagnosis of CMPA is made, which is in contrast with current nutrition guidelines in preterm infants. We strongly advocate that human milk with mothers on a cow's milk-free diet is the first choice of feed after the diagnosis of CMPA. Prospective studies are necessary to obtain more information regarding clinical presentation, diagnostic tools, and therapeutic approaches.

Allergic Proctocolitis: Literature Review and Proposal of a Diagnostic-Therapeutic Algorithm.

Allergic proctocolitis (AP) is a benign condition, frequent in childhood, that is classified as a non-IgE-mediated food allergy. The prevalence is unknown; however, its frequency appears to be increasing, especially in exclusively breastfed infants. Clinical manifestations typically begin in the first few months of life with the appearance of bright red blood (hematochezia), with or without mucus, in the stool of apparently healthy, thriving infants. Most cases of AP are caused by cow's milk proteins; however, other allergens, such as soy, egg, corn, and wheat, may be potential triggers. Diagnosis is based on the patient's clinical history and on the resolution of signs and symptoms with the elimination of the suspected food antigen from the diet and their reappearance when the food is reintroduced into the diet. The treatment of AP is based on an elimination diet of the trigger food, with resolution of the symptoms within 72-96 h from the beginning of the diet. The prognosis of AP is good; it is a self-limiting condition, because most children can tolerate the trigger food within one year of life, with an excellent long-term prognosis. The purpose of this review is to provide an update on the current knowledge and recommendations in epidemiological, diagnostic, and therapeutic terms to the pediatricians, allergists, and gastroenterologists who may find themselves managing a patient with AP.

A different starting line for allergic march: food protein-induced allergic proctocolitis.

OBJECTIVE: The aim of this study is to investigate the long-term prognosis of food protein--induced allergic proctocolitis (FPIAP) patients, the risk of developing both allergic and gastrointestinal diseases, and to evaluate whether it leads to allergic march. METHODS: A total of 149 children who were diagnosed with FPIAP and developed tolerance at least 5 years prior to the study and 41 children (with no history of food allergy) as a control group were enrolled. Both groups were re-evaluated for allergic diseases as well as gastrointestinal disorders. RESULTS: The mean age of diagnosis for the FPIAP group was 4.2 ± 3.0 months, while the mean age of tolerance was 13.9 ± 7.7 months. The mean age of both FPIAP and control groups at the last visit was 101.6 ± 24.4 and 96.3 ± 24.1 months, respectively (P = 0.213). At the final evaluation of both groups, the comorbid allergic disease was significantly higher in the FPIAP group (P < 0.001). There was no significant difference between the two groups in terms of functional gastrointestinal disorders (FGIDs), eosinophilic gastrointestinal diseases, and inflammatory bowel disease (P = 0.198, 0.579, and 0.579, respectively).In the FPIAP group, the allergic disease was significantly higher at the final visit in patients with comorbid allergic disease at diagnosis (P < 0.001). In the FPIAP group, FGID was significantly higher in the group that developed allergic diseases in the future, compared to the group that did not develop allergic diseases in the future (P = 0.034). The proportion of both FGID and allergic diseases was significantly higher in subjects that developed tolerance at >18 months, compared to subjects that developed tolerance at >18 months (P < 0.001 and <0.001, respectively). CONCLUSIONS: Patients with FPIAP may develop allergic diseases as well as FGID in the long term.

[Biotherapies for the treatment of ulcerative colitis]. / Biothérapies dans le traitement de la rectocolite hémorragique.

BIOTHÉRAPIES DANS LE TRAITEMENT DE LA RECTOCOLITE HÉMORRAGIQUE. Le traitement de la rectocolite hémorragique a considérablement évolué puisqu'il doit, pour la plupart des patients,permettre une cicatrisation des lésions inflammatoires coliques et non plus une simple rémission des symptômes cliniques. Ceci est désormais possible grâce aux biothérapies dont trois classes principales sont autorisées dans la rectocolite hémorragique. Les anti-TNF, classe la plus ancienne, ont fait la preuve de leur efficacité et peuvent être utilisés en première ligne de traitement après échec des traitements conventionnels. Parmi eux, seul l'infliximab est recommandé dans les colites aiguës graves. Le védolizumab, anti-intégrine, peut également être utilisé en première ligne, avec un excellent profil de tolérance mais pas d'effet sur les manifestations extradigestives. Les anti-interleukines 12 et 23 (ustékinumab), bientôt rejointes par d'autres anticorps spécifiques de l'interleukine 23, sont également très efficaces et leur tolérance excellente, mais se positionnent en échec d'une première ligne de biothérapie. S'ajoutent à cet arsenal les inhibiteurs de JAK, petites molécules orales, d'action très puissante mais dont le profil médiocre de tolérance les réserve aux sujets jeunes, sans comorbidité et généralement après échec de deux lignes de biothérapie. Tous ces traitements sont actuellement disponibles à domicile, par voie sous-cutanée, ou orale pour les inhibiteurs de JAK. Ceci implique pour les patients une bonne connaissance, acquise par l'éducation thérapeutique, et la mise en place d'un suivi coordonné avec tous les acteurs de soins : gastroentérologues, médecins généralistes et infirmières de coordination.

BIOTHERAPIES FOR THE TREATMENT OF ULCERATIVE COLITIS. The treatment of ulcerative colitis has evolved considerably since it must, for most patients, allow healing of inflammatory colonic lesions and no longer a simple remission of clinical symptoms. This is now possible thanks to biotherapies, of which three main classes are authorized in ulcerative colitis. Anti-TNFs, the oldest class, have proven their effectiveness and can be used as first-line treatment after failure of conventional treatments. Among them, only infliximab is recommended in severe acute colitis. Vedolizumab, anti-integrin, can also be used in first line with an excellent safety profile but no effect on extradigestive manifestations. The anti-interleukin 12/23 ustekinumab, soon joined by other antibodies specific for interleukin 23, is also very effective and its tolerance excellent, but is positioned after a failure of a first biologic. Janus kinase (JAK) inhibitors, small oral molecules, with a very powerful action, but whose poor tolerance profile reserves them for young subjects, without comorbidity and generally after failure of two lines of biologics. All these treatments are currently available at home, by subcutaneous route, or orally for JAK inhibitors. This implies their good knowledge and the implementation of patient follow-up coordinated with all healthcare providers: gastroenterologists, general practitioners and IBD coordinating nurses.

British Association of Sexual Health and HIV (BASHH) United Kingdom national guideline for the management of sexually transmitted enteric infections 2023.

This is the first British Association of Sexual Health and HIV (BASHH) national guideline for the management of sexually transmitted enteric infections (STEI). This guideline is primarily aimed for level 3 sexual health clinics; however, it may also be applicable to other settings such as primary care or other hospital departments where individuals with STEI may present. This guideline makes recommendations on testing, management, partner notification and public health control of STEI.

Outcomes reported in randomized controlled trials for mixed and non-IgE-mediated food allergy: Systematic review.

BACKGROUND: Mixed and non-IgE-mediated food allergy is a subset of immune-mediated adverse food reactions that can impose a major burden on the quality of life of affected patients and their families. Clinical trials to study these diseases are reliant upon consistent and valid outcome measures that are relevant to both patients and clinicians, but the degree to which such stringent outcome reporting takes place is poorly studied. OBJECTIVE: As part of the Core Outcome Measures for Food Allergy (COMFA) project, we identified outcomes reported in randomized clinical trials (RCT) of treatments for mixed or non-IgE-mediated food allergy. DESIGN: In this systematic review, we searched the Ovid, MEDLINE and Embase databases for RCTs in children or adults investigating treatments for food protein-induced enterocolitis syndrome, food protein-induced allergic proctocolitis, food protein-induced enteropathy and eosinophilic gastrointestinal disorders including eosinophilic esophagitis [EoE], eosinophilic gastritis and eosinophilic colitis published until 14 October 2022. RESULTS: Twenty-six eligible studies were identified, with 23 focused on EoE (88%). Most interventions were corticosteroids or monoclonal antibodies. All EoE studies assessed patient-reported dysphagia, usually using a non-validated questionnaire. Twenty-two of 23 EoE studies used peak tissue eosinophil count as the primary outcome, usually using a non-validated assessment method, and other immunological markers were only exploratory. Thirteen (57%) EoE studies reported endoscopic outcomes of which six used a validated scoring tool recently recommended as a core outcome for EoE trials. Funding source was not obviously associated with likelihood of an RCT reporting mechanistic versus patient-reported outcomes. Only 3 (12%) RCTs concerned forms of food allergy other than EoE, and they reported on fecal immunological markers and patient-reported outcomes. CONCLUSIONS: Outcomes measured in clinical trials of EoE and non-IgE-mediated food allergy are heterogeneous and largely non-validated. Core outcomes for EoE have been developed and need to be used in future trials. For other forms of mixed or non-IgE-mediated food allergies, core outcome development is needed to support the development of effective treatments. SYSTEMATIC REVIEW REGISTRATION: OSF public registry DOI:10.17605/OSF.IO/AZX8S.

Children with Delayed-Type Cow's Milk Protein Allergy May Be at a Significant Risk of Developing Immediate Allergic Reactions Upon Re-introduction.

Background: Cow's Milk Protein Allergy (CMPA) is the most common food allergy in children. The reaction is classified into IgE-mediated immediate reaction and delayed-onset, according to the underlying immune mechanism, and hence, the timing of the symptoms. Case reports suggest that children, with delayed CMPA reactions on elimination diet, may develop severe immediate reactions on reintroduction. Aim: The objective of this study was to evaluate the incidence and the risk factors of developing immediate reactions to milk and dairy products in children with CMPA whose initial presentations were of delayed type. Methods: A retrospective chart review of children, aged 0-12 years, presented with delayed type CMPA reactions to the allergy-clinical immunology clinics, was performed. The diagnosis was made clinically, and with appropriate allergy tests when indicated. Results: Sixty children were included. Males:female ratio was 1.7:1. Family history of atopy was in 72%, and 57% had personal history of atopy. Sixty percent were not breast fed. The most common concomitant food allergy was egg. The most common initial presentation was diarrhea without protein loss or bleeding followed by exacerbation of atopic dermatitis upon exposure to dairy products. Immediate reactions developed in 21.6% upon re-exposure. There were significant associations with concomitant food allergy (OR 56.6 (3.15-1016.1) P<0.0001), especially eggs (OR 12.85 (3.09-53.5) P<0.01). Conclusion: Children with CMPA, who present with delayed-type allergic reactions, may be at a significant risk of developing immediate reactions upon reintroduction. Evaluation of possible IgE-mediated allergic reactions before reintroduction may be advisable.

Perspectives on Non-IgE-Mediated Gastrointestinal Food Allergy in Pediatrics: A Review of Current Evidence and Guidelines.

Food allergy is an immune-mediated disease that can result in considerable morbidity and even mortality, with a significant negative impact on patients' quality of life. It is characterized by allergic symptoms that can occur shortly after a relevant food allergen ingestion, or can be delayed or chronic, which make it more difficult for diagnosis. The symptoms of this disease can range from mild to severe, and rarely can cause anaphylaxis, a life-threatening allergic reaction. The prevalence of non-immunoglobulin E (IgE)-mediated food allergy is poorly established outside of cow's milk allergy, with an adjusted incidence ranging between 0.13% and 0.72%. Several disorders are classified as non-immunoglobulin E (IgE)-mediated food allergies that predominantly affect the gastrointestinal tract including food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), food protein-induced allergic enteropathy (FPE), and food protein-induced dysmotility disorders (GORD and constipation). Eosinophilic esophagitis (EoE) is listed in this group, even though it considered by some authorities to be mixed reaction with both IgE and cell-mediated immune response to be involved in the reaction. The most common types of non-IgE-mediated food allergy are food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). These disorders typically present in infancy and are often triggered by cow's milk protein. Patients with FPIES present with profuse emesis and dehydration, while FPIAP patients present with hematochezia in otherwise healthy infants. Since there are no specific confirmatory non-invasive diagnostic laboratory tests, the diagnosis is usually made clinically when typical symptoms improve upon the removal of the culprit food. Food reintroduction should be attempted, when possible, with documentation of symptoms of relapse to confirm the diagnosis. The management includes dietary avoidance, supportive treatment in the case of accidental exposure, and nutritional counseling. This review focuses on the clinical manifestations, epidemiology, management, and recent guidelines of the most common non-IgE-mediated food hypersensitivity disorders (FPIES, FPIAP, and FPE).

Dietary Factors May Delay Tolerance Acquisition in Food Protein-Induced Allergic Proctocolitis.

BACKGROUND: Dietary and environmental factors may influence tolerance acquisition in food protein-induced allergic proctocolitis (FPIAP). This retrospective observational study explored the role of maternal diet during pregnancy and breastfeeding in tolerance acquisition in infantile FPIAP. METHODS: Breastfed infants with FPIAP from six diverse regions in Greece were divided into two groups, based on development of tolerance to the trigger food: Group A (n = 43), before, and Group B (n = 53), after, the 6th month of age. Maternal diet during pregnancy and breastfeeding was elicited using the Mediterranean Diet Score Questionnaire and the Mediterranean Oriented Culture Specific Semi-Quantitative Food Frequency Questionnaire. RESULTS: Mean age at diagnosis of FPIAP (1.5 months) and weaning (5.5 months) were the same in both groups. The main trigger was cow's milk. Group A received infant milk formula earlier than Group B. Group B had a higher incidence of asthma/wheeze, siblings with milk allergy, maternal smoking and rural residence. On multivariate analysis, earlier resolution of FPIAP was associated with higher maternal education and with salt intake and consumption of goat/sheep cheese during pregnancy and olive oil during breastfeeding. Consumption of multivitamins during pregnancy and meat, winter fruits, green vegetables, butter, salt, "ready-to-eat" meals and pastries during breastfeeding were correlated with longer duration of symptoms. CONCLUSIONS: Mothers of children with FPIAP to cow's milk protein can be advised to eat more yogurt, cheese and olive oil during subsequent pregnancies, and avoid multivitamins, grilled food, "ready-to-eat" meals, pastries, meat and alcohol during breastfeeding, to reduce the duration of FPIAP presenting in future infants.

Assessment of intracellular zinc levels in infants with food protein-induced allergic proctocolitis.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is characterized by bloody stools in well-appearing infants. Zinc is a micronutrient that plays a crucial role in immune modulation and is essential for cellular function during immune response. Although there are studies on the assessment of intracellular zinc levels in allergic diseases, no data is available on erythrocyte zinc levels of patients with FPIAP. OBJECTIVE: This study aimed to assess the erythrocyte zinc levels of children with allergic proctocolitis and compare zinc levels with clinical and demographic characteristics. METHODS: This was a case-control study that prospectively compared 50 patients with FPIAP and 50 healthy children without malnutrition. The erythrocyte zinc levels of children were determined using atomic absorption spectrophotometry. RESULTS: Fifty patients with FPIAP, including 28 (51%) girls, with median age of 7.1 ± 2.9 (3-14) months and 50 healthy children, including 26 (53.1%) girls, with median age of 7.7 ± 2.8 (3-13) months were included in the study. Seventy percent (n = 35) of the patients with FPIAP started to have symptoms while they were exclusively breastfeeding. Offending allergen foods were cow's milk (78%), egg (40%), sesame (10%), hazelnut (8%), almond (6%), beef (6%), and peanuts (6%, n = 3). Intracellular (erythrocyte) zinc levels in patients with FPIAP were lower than in the healthy control group (495.5 ± 134 µg/dL, 567.3 ± 154.4 µg/dL, respectively, P = 0.01). Patients with FPIAP aged younger than 6 months had lower intracellular zinc levels compared with those aged above 6 months (457 ± 137 µg/dL; 548 ± 112 µg/dL, respectively, P = 0.01). There was no relationship between zinc levels and time of symptom onset, presence of concomitant disease, being allergic to multiple foods, and family history of atopy (P > 0.05). CONCLUSIONS: FPIAP is a food allergy with limited information on its pathogenesis. Considering the beneficial effects on gastrointestinal system epithelia, zinc may be involved in the pathogenesis of FPIAP. Future comprehensive prospective research on this subject is of importance.

Assessment of intracellular zinc levels in infants with food protein–induced allergic proctocolitis

Background: Food protein–induced allergic proctocolitis (FPIAP) is characterized by bloody stools in well-appearing infants. Zinc is a micronutrient that plays a crucial role in immune modulation and is essential for cellular function during immune response. Although there are studies on the assessment of intracellular zinc levels in allergic diseases, no data is available on erythrocyte zinc levels of patients with FPIAP. Objective: This study aimed to assess the erythrocyte zinc levels of children with allergic proctocolitis and compare zinc levels with clinical and demographic characteristics. Methods: This was a case–control study that prospectively compared 50 patients with FPIAP and 50 healthy children without malnutrition. The erythrocyte zinc levels of children were determined using atomic absorption spectrophotometry. Results: Fifty patients with FPIAP, including 28 (51%) girls, with median age of 7.1 ± 2.9 (3–14) months and 50 healthy children, including 26 (53.1%) girls, with median age of 7.7 ± 2.8 (3–13) months were included in the study. Seventy percent (n = 35) of the patients with FPIAP started to have symptoms while they were exclusively breastfeeding. Offending allergen foods were cow’s milk (78%), egg (40%), sesame (10%), hazelnut (8%), almond (6%), beef (6%), and peanuts (6%, n = 3). Intracellular (erythrocyte) zinc levels in patients with FPIAP were lower than in the healthy control group (495.5 ± 134 µg/dL, 567.3 ± 154.4 µg/dL, respectively, P = 0.01). Patients with FPIAP aged younger than 6 months had lower intracellular zinc levels compared with those aged above 6 months (457 ± 137 µg/dL; 548 ± 112 µg/dL, respectively, P = 0.01). There was no relationship between zinc levels and time of symptom onset, presence of concomitant disease, being allergic to multiple foods, and family history of atopy (P > 0.05). Conclusions: FPIAP is a food allergy with limited information on its pathogenesis (AU)

Cultural adaptation and validation of the Spanish version of the Cow's Milk-related Symptom Score (CoMiSS) for cow's milk protein allergy.

INTRODUCTION AND AIMS: The prevalence of cow's milk protein allergy in the first year of life varies from 1.8 to 7.5%. The Cow's Milk-related Symptom Score (CoMiSS) was published in 2014 and facilitates the diagnosis of cow's milk protein allergy. It is not meant to replace the clinical diagnosis, but rather to guide the treating team in the diagnostic process and reduce unnecessary diets. The aim was to translate the CoMiSS from English to Spanish and culturally adapt and validate the resulting Spanish version. MATERIALS AND METHODS: An adaptation and validation study on the CoMiSS questionnaire was carried out in two phases: First, the CoMiSS was translated from English to Spanish, after which interrater reliability of the translated score was assessed. Second, interrater reliability tests were carried out on 32 pediatric patients under 7 years of age that were treated for the first time at the Food Allergy Clinic of the Hospital Italiano de Buenos Aires, were suspected of having cow's milk protein allergy, and had not received any treatment, within the time frame of May 2018 and May 2019. RESULTS: Thirty-two patients were evaluated, 14 of whom were females (45%), and the median patient age was 3 months (IQR 2-4). The median result of the first measurement of the scale was 7.0 (IQR 4.5-9.0) and the median of the second measurement was 5.0 (IQR 4.0-8.0). The final intraclass correlation coefficient was 0.80 (95% CI 0.63-0.9). CONCLUSION: The Spanish translation of the CoMiSS was comparable to the original English version, with excellent interrater reliability. This simple and little-known tool has the benefit of being a noninvasive, rapid, reliable, and easy-to-use strategy.

A different starting line for allergic march: food protein-induced allergic proctocolitis

Objective: The aim of this study is to investigate the long-term prognosis of food protein--induced allergic proctocolitis (FPIAP) patients, the risk of developing both allergic and gastrointestinal diseases, and to evaluate whether it leads to allergic march. Methods: A total of 149 children who were diagnosed with FPIAP and developed tolerance at least 5 years prior to the study and 41 children (with no history of food allergy) as a control group were enrolled. Both groups were re-evaluated for allergic diseases as well as gastrointestinal disorders. Results: The mean age of diagnosis for the FPIAP group was 4.2 ± 3.0 months, while the mean age of tolerance was 13.9 ± 7.7 months. The mean age of both FPIAP and control groups at the last visit was 101.6 ± 24.4 and 96.3 ± 24.1 months, respectively (P = 0.213). At the final evaluation of both groups, the comorbid allergic disease was significantly higher in the FPIAP group (P < 0.001). There was no significant difference between the two groups in terms of functional gastrointestinal disorders (FGIDs), eosinophilic gastrointestinal diseases, and inflammatory bowel disease (P = 0.198, 0.579, and 0.579, respectively). In the FPIAP group, the allergic disease was significantly higher at the final visit in patients with comorbid allergic disease at diagnosis (P < 0.001). In the FPIAP group, FGID was significantly higher in the group that developed allergic diseases in the future, compared to the group that did not develop allergic diseases in the future (P = 0.034). The proportion of both FGID and allergic diseases was significantly higher in subjects that developed tolerance at >18 months, compared to subjects that developed tolerance at >18 months (P < 0.001 and <0.001, respectively). Conclusions: Patients with FPIAP may develop allergic diseases as well as FGID in the long term (AU)

[Classification of food allergy: generalities]. / Clasificación de la alergia alimentaria: generalidades.

The prevalence of food allergy has increased in some regions of the world, and with it the incidence, according to geographical variability, in the phenotype and clinical manifestations. Food allergy arises from the specific immune response induced by exposure to the proteins of a certain food. Food intolerance refers to non-immune reactions, caused by unique physiological characteristics of the individual, including metabolic, toxic, pharmacological and undefined mechanisms. Adverse reactions to foods are classified as: IgE-mediated: Type I Hypersensitivity, non-IgE-mediated: Type IV Hypersensitivity, mixed: Types I and IV Hypersensitivity Non-Allergic; toxic, pharmacological, metabolic, intolerances. These types of alterations are rare but have increased in recent years; These include protein-induced enterocolitis syndrome, which can cause emesis, diarrhea and hypotension, and shock, which begins two hours after ingestion of the allergen. Protein-induced allergic proctocolitis is a condition that includes allergy to cow's milk protein. Delayed reactions usually affect the digestive system, are more insidious in their onset and are not immediately controlled, even with the suspension of food. There are eight foods responsible for 90% of food allergies: milk, eggs, soy, wheat, peanuts, walnuts, fish, and shellfish.

La prevalencia de alergia alimentaria se ha incrementado en algunas regiones del mundo, y con ello la incidencia, según la variabilidad geográfica, en el fenotipo y manifestaciones clínicas. La alergia alimentaria surge de la respuesta inmune específica inducida por la exposición a las proteínas de cierto alimento. La intolerancia alimentaria se refiere a reacciones no inmunitarias, causadas por características fisiológicas únicas del individuo, que incluyen mecanismos metabólicos, tóxicos, farmacológicos e indefinidos. Las reacciones adversas a los alimentos se clasifican en: mediada por IgE: Hipersensibilidad Tipo I, no mediada por IgE: Hipersensibilidad Tipo IV, mixtas: Hipersensibilidad Tipos I y IV No Alérgicas; tóxicas, farmacológicas, metabólicas, intolerancias. Este tipo de alteraciones son poco frecuentes, pero se ha incrementado en los últimos años; entre estas se encuentra el síndrome de enterocolitis inducida por proteínas, que puede producir emesis, diarrea e hipotensión, y estado de shock, que inicia dos horas después de la ingestión del alergeno. La proctocolitis alérgica inducida por proteínas es una afectación que incluye la alergia a la proteína de leche de vaca. Las reacciones retardadas suelen afectar el aparato digestivo, son más insidiosas en su inicio y no se controlan inmediatamente, aún con la suspensión del alimento. Existen ocho alimentos responsables del 90% de alergia alimentaria: leche, huevo, soya, trigo, cacahuate, nuez, pescados y mariscos.