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.

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.

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.
CONCLUSIONS: 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.

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 (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.

There are conflicting associations reported between food allergies (FAs) and poor growth, with some indication that children with multiple FAs are at highest risk.
We analyzed longitudinal weight-for-length (WFL) trajectories from our healthy cohort to evaluate growth in children with IgE-mediated FAs and food protein-induced allergic proctocolitis (FPIAP), a non-IgE-mediated FA.
Our observational cohort of 903 healthy newborn infants was prospectively enrolled to evaluate the development of FAs. Longitudinal mixed effects modeling was used to compare differences in WFL among children with IgE-FA and FPIAP, compared with unaffected children, through age 2.
Among the 804 participants who met inclusion criteria, FPIAP cases had significantly lower WFL than unaffected controls during active disease, which resolved by 1 year of age. In contrast, children with IgE-FA had significantly lower WFL than unaffected controls after 1 year. We also found that children with IgE-FA to cow\'s milk had significantly lower WFL over the first 2 years of age. Children with multiple IgE-FAs had markedly lower WFL over the first 2 years of age.
Children with FPIAP have impaired growth during active disease in the first year of age which resolves, whereas children with IgE-FA, particularly those with multiple IgE-FA, have impaired growth more prominently after the first year of age. It may be appropriate to focus nutritional assessment and interventions accordingly during these higher risk periods in these patient populations.

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).

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.

BACKGROUND: Some aspects of diagnostic elimination/challenge diets in food protein-induced allergic proctocolitis (FPIAP) are still poorly defined.
OBJECTIVE: This study investigated the symptom spectrum, time required for resolution of each symptom, triggering foods, and risk factors for multiple food allergies (MFA) in FPIAP.
METHODS: Infants referred with visible blood in stool were enrolled after etiologies other than FPIAP had been excluded. Laboratory evaluation, clinical features, and elimination/challenge steps were performed prospectively during diagnostic management.
RESULTS: Ninety-one of 102 infants (53 boys) were diagnosed with FPIAP. Eleven children did not bleed during challenges. Visible blood in stool began before 2 months of age in 63.6% of the infants not diagnosed with FPIAP, compared with 18.9% of the patients with FPIAP (P = .003). Offending foods were identified as cow\'s milk (94.5%), egg (37.4%), beef (10.9%), wheat (5.5%), and nuts (3.3%). MFA was determined in 42.9% of patients. Multivariate logistic regression analysis identified atopic dermatitis (AD) (odds ratio [OR]: 2.98, 95% confidence interval [CI]: 1.18-7.55, P = .021) and an eosinophil count ≥300 cells/μL (OR: 2.72, 95% CI: 1.09-6.80, P = .032) as independent risk factors for MFA. Blood and mucus in stool disappeared in a median 3 days (interquartile range [IQR]: 1-14.5 days) and 30 days (IQR: 8-75 days), respectively.
CONCLUSIONS: A tendency to transient bleeding occurs in infants who present with bloody stool before 2 months of age. A 2-week duration of elimination for blood in stool is sufficient to reach a judgment of suspected foods for FPIAP. Mucus in stool is the last symptom to disappear. Concurrent AD suggests a high probability of MFA in FPIAP.

BACKGROUND: Anal skin tags are commonly seen with anal fissures, haemorrhoids, inflammatory bowel disease and their association have been extensively studied. However the presence of anal skin tag in food protein-induced allergic proctocolitis has rarely been reported in literature. We report a neonate with food protein-induced allergic proctocolitis who presented with blood in stool and anal skin tag.
METHODS: A 26-day-old baby presented with history of passing intermittent blood in stools for two days. The baby was exclusively breast-fed and was well-appearing with no failure to thrive. Two anal skin tags were present but there was no evidence of anal fissures or haemorrhoids. The biopsy of anal skin tag showed fibroepithelial polyp. Colonoscopy was suggestive of food protein-induced allergic proctocolitis. In view of poor response to elimination diet in the mother and extensively hydrolysed formula, the baby was started on amino acid formula with complete recovery.
CONCLUSIONS: Through this case we wish to highlight that clinicians should consider food protein-induced allergic proctocolitis in their differential diagnosis in a neonate presenting with blood in stools and anal skin tag.