Gastrointestinal manifestations of food allergy in infants: clinical forms, diagnostics, and prognosis

Relevance

Food allergy represents a significant medical and social problem, particularly in pediatric practice. The prevalence of cow's milk protein (CMP) allergy in young children reaches 1.9-4.9%, making it the most common form of food allergy in this age group [1, 2].

Gastrointestinal manifestations of food allergy are of particular clinical importance, as they can be the sole symptom of the disease, significantly complicating timely diagnosis. Non-IgE-mediated forms of food allergy (food protein-induced proctocolitis, enterocolitis, enteropathy) present with diverse clinical manifestations depending on the child's age and the localization of the pathological process, necessitating a differentiated approach to diagnosis and treatment [3, 4].

The relevance of the problem is further underscored by the fact that the digestive tract is the primary target of allergic reactions and the site of food allergen penetration. Moreover, the clinical picture of gastrointestinal food allergies is often non-specific and can mimic other gastrointestinal disorders, leading to diagnostic errors and inadequate therapy [5, 6].

The study of prognostic factors for the disease course is of particular significance. It has been established that children with food allergy have a four-fold higher risk of developing other atopic diseases (bronchial asthma, allergic rhinitis, atopic dermatitis) compared to children without food allergy. Notably, isolated gastrointestinal non-IgE-mediated forms of CMP allergy are characterized by a more favorable prognosis and earlier development of tolerance. Despite significant progress in understanding the pathophysiological mechanisms of food allergy, the age-related characteristics of clinical manifestations, morphological features of various forms of gastrointestinal food allergy, as well as optimal diagnostic and treatment algorithms for this pathology in young children remain insufficiently studied [7, 8].

Thus, a comprehensive study of the clinical and morphological features of gastrointestinal forms of food allergy in young children, the development of differentiated diagnostic approaches, and the identification of prognostic factors for the disease course are of considerable scientific and practical interest and define the relevance of this research.

Objective

To study the clinical and morphological features of various forms of gastrointestinal manifestations of food allergy in young children, to determine the age-related characteristics of manifestation, to evaluate the effectiveness of diagnostic approaches and an elimination diet, and to identify prognostic factors for the development of tolerance to cow's milk protein.

Materials and Methods

This study presents an analysis of clinical cases of food allergy with gastrointestinal manifestations in young children, observed between 2023 and 2025 in polyclinics and private centers in the city of Yaroslavl. The study included patients aged from 2 weeks to 2 years with a confirmed diagnosis of CMP allergy, presenting primarily with gastrointestinal symptoms.

Diagnosis of gastrointestinal food allergy forms was based on a comprehensive assessment of anamnestic data, clinical presentation, results of laboratory and instrumental investigations, and the response to an elimination diet.

The research methods included: a detailed collection of medical history with a focus on feeding type (breastfeeding, formula), timing of symptom onset, and family history of atopic diseases; assessment of physical development using centile charts; coprological examination to identify signs of inflammatory changes, steatorrhea, amylorrhea, and creatorrhea; measurement of fecal calprotectin levels as a marker of intestinal inflammation; allergological testing (skin prick tests) to exclude IgE-mediated mechanisms; in select cases, morphological examination of intestinal mucosal biopsies was performed; evaluation of the effectiveness of an elimination diet (exclusion of CMP-containing products from the mother's diet during breastfeeding or transition to specialized hydrolyzed formulas for formula-fed infants).

Based on clinical and laboratory data, all cases were classified into three main forms of gastrointestinal food allergy:

• Food Protein-Induced Allergic Proctocolitis (FPIAP);

• Food Protein-Induced Enterocolitis Syndrome (FPIES);

• Food Protein-Induced Enteropathy (FPE).

For each form, an analysis of age-specific features of manifestation, characteristic clinical presentations, laboratory parameters, and the effectiveness of the elimination diet was conducted. Particular attention was paid to the timing of tolerance development to CMP and prognostic factors for a persistent disease course.
Descriptive statistics methods were used to process the obtained data to identify patterns and correlations using Stattech software (Kazan). The study was conducted in accordance with the ethical principles of the Helsinki Declaration. All participants provided informed consent. Data were anonymized to ensure confidentiality.

Results and Discussion

The study involved an analysis of clinical cases of children with various forms of gastrointestinal manifestations of cow's milk protein (CMP) allergy. Representative clinical observations illustrating the main forms of this pathology are presented below.

Food Protein-Induced Allergic Proctocolitis (FPIAP)
Clinical Case 1
A 3-week-old, breastfed infant was admitted to the neonatal pathology department with complaints of blood in the stool. History: First pregnancy, first delivery. Pregnancy was uneventful; delivery at 39 weeks, birth weight 3200 g, length 51 cm, mild birth asphyxia, APGAR 6/7. Exclusively breastfed since birth. Examination on admission: normal physical development. Skin clear, pink. Internal organs unremarkable. Abdomen soft, palpable in all quadrants. Liver +1 cm. Spleen not palpable. Umbilical area epithelialized, urine clear. Anus closed, no fissures. Stool passed in small portions 7-8 times per day, yellow and pasty with transparent mucus and streaks of blood in the mucus; some portions contained small specks of blood. Coproscopy revealed 10-12 red blood cells per field of view. Fecal calprotectin level was moderately elevated (180 µg/g). After the mother was switched to a dairy-free diet, the symptoms resolved completely within 72 hours.
This case demonstrates a typical presentation of FPIAP with early manifestation (2-6 weeks of life), preserved normal physical development, and a rapid response to an elimination diet. It is noteworthy that approximately 50% of FPIAP cases are observed in breastfed infants, confirming the possibility of sensitization through breast milk.

Food Protein-Induced Enterocolitis Syndrome (FPIES)
Clinical Case 2
A 2.5-month-old infant on mixed feeding was admitted with complaints of diarrhea with mucus and blood, and insufficient weight gain. Coproscopy revealed steatorrhea, amylorrhea, creatorrhea, and microscopic changes: leukocytes up to 20-30 per field of view, erythrocytes up to 15 per field of view. Fecal calprotectin level was 360 µg/g. Given the clinical presentation, a colonoscopy was performed to rule out surgical pathology, revealing the following changes: crypt abscesses and pronounced inflammatory cell infiltration of the colonic mucosa. After transitioning to a highly hydrolyzed formula, positive dynamics were observed: stool normalized, intestinal bleeding ceased, and weight gain improved.
This observation illustrates a classic case of FPIES with manifestation in the first 3 months of life, impaired physical development, and characteristic coproscopic findings.

Food Protein-Induced Enteropathy (FPE)
Clinical Case 3
A 7-month-old, formula-fed infant on a standard milk-based formula was admitted with complaints of chronic diarrhea, vomiting, insufficient weight gain, and abdominal distention. Examination revealed signs of malnutrition and an enlarged abdomen. Coproscopy showed steatorrhea, creatorrhea, and amylorrhea without inflammatory changes. Fecal calprotectin was within the normal range. An esophagogastroduodenoscopy (EGD) was performed, which revealed no obvious endoscopic changes; however, morphological examination of small intestinal mucosal biopsies showed atrophic enteritis with villous atrophy, crypt hyperplasia, and an increased number of eosinophils in the mucosal and submucosal layers. After transitioning to a highly hydrolyzed formula, positive dynamics were noted: stool normalized, vomiting ceased, and weight gain improved.
This case demonstrates a typical presentation of FPE with manifestation after 4 months of age, a pronounced malabsorption syndrome, and characteristic morphological changes in the small intestinal mucosa.

The analysis of clinical cases confirms the existence of various forms of gastrointestinal manifestations of CMP allergy, each with characteristic age-related features of manifestation and clinical presentation. CMP-induced proctocolitis (FPIAP) most often manifests at 2-6 weeks of age and is characterized by blood in the stool with preserved normal physical development. CMP-induced enterocolitis (FPIES) typically develops in children under 3 months of age and presents with diarrhea containing blood and mucus, as well as impaired physical development. CMP-induced enteropathy (FPE) occurs predominantly after 4 months of age and is characterized by a typical malabsorption syndrome. It is important to note that all described forms of gastrointestinal food allergy are non-IgE-mediated reactions, as confirmed by negative skin test results. This is consistent with literature data indicating that approximately 20% of CMP allergy cases follow a non-IgE-mediated mechanism.

In all observed cases, the cornerstone of therapy was an elimination diet. For breastfed infants, the exclusion of CMP-containing products from the mother's diet was recommended. For formula-fed infants or those requiring supplementation, a key therapeutic step for the majority of patients was the transition to a specialized therapeutic formula, which demonstrated high clinical efficacy and safety.

Follow-up of patients over time showed that the prognosis for gastrointestinal forms of CMP allergy is generally favorable. According to our data, isolated gastrointestinal (non-IgE-mediated) forms of CMP allergy are characterized by earlier development of tolerance compared to IgE-mediated food allergies. In FPIAP and FPIES, tolerance to CMP developed predominantly by 3 years of age, as confirmed by successful provocation tests. In FPE, tolerance development was noted somewhat later but still in the majority of cases before children reached 5 years of age.

It is important to emphasize that, despite the favorable prognosis regarding the development of tolerance to CMP, the risk of developing other atopic diseases (bronchial asthma, allergic rhinitis, atopic dermatitis) is four times higher in children with food allergy compared to children without food allergy, necessitating long-term follow-up for this patient category.

Conclusions

This study of gastrointestinal manifestations of cow's milk protein allergy in young children revealed characteristic clinical and laboratory features of three main forms of this pathology: food protein-induced allergic proctocolitis (FPIAP), food protein-induced enterocolitis syndrome (FPIES), and food protein-induced enteropathy (FPE). It was established that each form has its own age-related characteristics of manifestation, distinct clinical presentations, and prognostic factors.

The use of a highly hydrolyzed formula as therapeutic nutrition for all forms of gastrointestinal food allergy demonstrated high clinical efficacy. The composition of the formula, which includes extensively hydrolyzed whey protein, medium-chain triglycerides, nucleotides, human milk oligosaccharides (2'FL and LNnT), and specific fatty acids, not only ensures rapid symptom resolution but also promotes the restoration of the intestinal mucosal structure and the development of food tolerance.