Search Results (25)

Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated gastrointestinal food allergy. Although tolerance to the culprit food is usually achieved within the first year of life, late acquisition occurs and remains poorly predictable. This study aimed to analyze clinical characteristics and explore factors that may potentially function as predictors of late tolerance acquisition to cow’s milk (CM). Methods: We conducted a cross-sectional study at two Italian pediatric clinics (2020–2024), including infants diagnosed with FPIAP. Clinical, dietary, and immunological variables; onset and duration of rectal bleeding (visible blood in the stools); and time to CM tolerance were analyzed. Late tolerance was defined as acquisition after 19 months according to the distribution of tolerance achievement in our population. Statistical analyses included χ², Mann–Whitney U, Spearman’s correlation, and logistic regression. Results: Ninety-four infants were included (median age at onset 2.9 months [IQR 1.9–4.7]); 58 (62%) were exclusively breastfed and 18 (19%) were born preterm (<37 completed weeks of gestation). CM was the culprit food in all cases; tolerance was achieved in all infants at a median age of 12 months. Family history of atopy and atopic dermatitis were reported in 44% and 19% of infants, respectively. Late CM tolerance was associated with preterm birth, fortification of human milk, early antibiotic exposure, growth faltering, and recurrent infections. Logistic regression identified family history of atopy (OR 5.4 [95% CI 1.2–25.4]; p = 0.031), atopic dermatitis (OR 8.2 [1.7–40.7]; p = 0.010), rectal bleeding >18 days before elimination diet (OR 5.9 [1.3–27.7]; p = 0.023), and IgE sensitization (OR 6.4 [1.2–35.0]; p = 0.034) as factors that may potentially function as predictors of late tolerance acquisition to CM. Conclusions: Identification of factors that may potentially function as predictors of late tolerance acquisition to CM in infants with FPIAP may help providing a personalized clinical management for these patients. Full article

Background/Objectives: Cow’s milk allergy (CMA) manifests with various clinical syndromes and has a wide range of symptoms in infants. This study aims to investigate the prevalence, clinical presentation, and outcome of clinical types and subtypes of CMA diagnosed in children within the first 12 months of life. Methods: Children with a CMA diagnosis were included in this mixed retrospective and prospective cohort study and were followed up for four years. Data recorded included clinical manifestations, feeding modes, and outcomes. Follow-up included oral cow’s milk (CM) challenge and/or elimination—reintroduction of CM, provided there was parental consent. Also, skin prick test and serum CM-specific IgE were assessed when needed. Results: A total of 93 infants (age: 3 days to 24 months) diagnosed with CMA were included. Prevalence was 28% for IgE-mediated CMA and 72%, 49.5%, 18.3%, and 3.7% for non-IgE-mediated CMA and its subtypes, Allergic Proctocolitis (AP), Food Protein induced Enteropathy (FPE), and Food Protein Induced Enterocolitis Syndrome (FPIES), respectively. Main manifestations were gastrointestinal (74%), skin rash (31%), failure to thrive (11.8%), feeding aversion (15.1%), respiratory symptoms (5.4%), and irritability/restlessness (9.7%). Follow-up revealed a high rate of AP and FPE tolerance within the first year, while FPIES and IgE-mediated CMA achieved tolerance at an older age. Conclusions: Our study demonstrated the predominance of AP and increased incidence of gastrointestinal involvement. Outcome was good for AP and FPE but less favorable for FPIES and IgE-mediated CMA. Our results, combined with published data, could increase our understanding of CMA-associated syndromes in infants and contribute to the guidance of effective management. Full article

Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-immunoglobulin-E-mediated allergic colitis. Most cases resolve after 1 year of age, but delayed resolution and growth retardation may occur in some refractory cases. We aimed to explore the clinical characteristics, treatment approaches, and outcomes of such pediatric patients. Methods: We retrospectively analyzed 35 patients with refractory FPIAP at our center between January 2015 and January 2025. Patients were categorized into early- and non-early-onset groups according to timing of symptom onset; various clinical data were collected and treatment regimens were monitored. Results: The proportion of patients with growth retardation was significantly higher in the non-early onset group than in the early-onset group (73.3% vs. 35.0%, p = 0.041), whereas hemoglobin levels were higher in the early-onset group (118.95 ± 11.26 g/L vs. 107.93 ± 14.61 g/L, p = 0.017).The proportion of corticosteroid use was significantly lower in the early-onset group (15.0% vs. 60.0%; p = 0.011). During follow-up, among 35 patients, 14 (40%) could not tolerate certain foods, including cow’s milk (100%), eggs (42.9%), and wheat (35.7%). Conclusions: Refractory FPIAP was protracted, with a higher incidence of growth retardation, lower hemoglobin levels, and higher corticosteroid use in the non-early onset group. The optimal treatment approach should be explored. Full article

Objective: The aim of our study was to investigate whether faecal concentrations of eosinophil cationic protein (fECP) and human β-defensins (HBD2s) are significantly elevated in children with cow’s milk-protein-induced allergic colitis (MPIAP) and whether a monthly milk-free diet reduces these markers. Materials and methods: This was a single-centre, prospective, observational cohort study involving 70 infants with MPIAP, aged 1–3 months, and 30 healthy controls of the same age. The concentrations of fECP and HBD2 were measured using the ELISA method (IDK^® Eosinophil Cationic Protein and β-Defensins ELISA Kit, Immunodiagnostik AG, Germany). Diagnosis of MPIAP was confirmed with an open milk challenge test. Results: The concentrations of fECP and HBD2 proved useful in evaluating MPIAP treatment with a milk-free diet, where the resolution of allergy symptoms and a significant (p = 0.0000) decrease in the concentrations of both biomarkers were observed after 4 weeks of following the diet. The concentrations of fECP and HBD2 were still higher than those in the control group. High concentrations of fECP can be helpful in diagnosing MPIAP (100% sensitivity), but the low specificity of the assay means that there is a risk of diagnosing MPIAP in one in six children who do not have the disease. The concentrations of HBD2 have low sensitivity, so one in four children with MPIAP will not be confirmed to have the disease using this indicator. Conclusions: fECP and HBD2 can be used to monitor the resolution of colitis in infants with MPIAP treated with a milk diet, indicating a slower resolution of allergic inflammation than the resolution of allergic symptoms. Therefore, neither of the parameters are useful for the diagnosis of MPIAP. Full article

Background: Cytomegalovirus (CMV) colitis is commonly seen in patients who are immunodeficient or have inflammatory bowel disease. Among the gastrointestinal sites affected by CMV, the colon is the most frequently affected, though rectal involvement is relatively rare. Reactivated CMV proctitis primarily occurs in elderly patients with comorbidities and is quite uncommon in immunocompetent individuals. Patients with reactivated CMV typically present with symptoms such as diarrhea, hematochezia, or tenesmus. Case presentation: We report a case of a female patient with uncontrolled diabetes who presented to the clinic complaining of perianal pain. She had no history of diarrhea or rectal bleeding. Lower GI endoscopy reported a small, localized, approximately 0.5 cm swelling in the proximal anal canal in addition to sigmoid diverticulosis. The biopsy revealed a small ulcer at the anorectal junction caused by CMV and confirmed by immunohistochemistry. Unfortunately, the patient was lost to follow-up before antiviral therapy could be initiated. Conclusions: This case highlights an uncommon presentation of reactivated CMV proctitis in an older diabetic patient presenting solely with perianal pain. Clinicians should maintain a high index of suspicion for CMV infection in elderly patients with comorbidities, even when classical colitis symptoms are absent, to avoid delayed diagnosis and management. Full article

Background: Cow-milk-induced allergic proctocolitis (CMIAP) is a non-IgE-mediated food hypersensitivity that often resolves spontaneously but may predispose infants to IgE-mediated allergies and eosinophilic gastrointestinal disorders. Understanding its pathophysiology is crucial for microbiota-based interventions. Methods: We enrolled 32 exclusively breastfed infants—16 with confirmed cases of CMIAP and 16 age-matched healthy controls. The cohorts were sex-balanced (8 F/8 M), term-born (gestational age ± SD: 40 ± 1.2 vs. 39 ± 1.3 weeks), vaginally delivered, and sampled at a mean age of 2.0 ± 0.44 months (range 1.5–3.0) vs. 2.4 ± 0.66 months (range 1.5–3.5). Faecal samples underwent 16S rRNA gene sequencing on the Illumina NovaSeq platform, with diversity and differential abundance analyses. Results: The maternal dairy intake was similar (total dairy: 250 ± 80 vs. 240 ± 75 mL/day; yoghurt: 2.3 ± 1.0 vs. 2.5 ± 1.2 days/week; p = 0.72). Bray–Curtis dissimilarity assessments revealed distinct microbiota in infants with CMIAP. Infants with CMIAP had a lower abundance of Bifidobacterium (log₂FC−2.27; q = 0.022; ANCOM-BC), Collinsella (−29.35; padj < 0.0001; DESeq2), and Limosilactobacillus (−8.01; padj = 0.0285; DESeq2; q < 0.0001; ANCOM-BC) compared with controls. In contrast, Hungatella (+24.99; padj < 0.0001; DESeq2), Veillonella (+4.73; padj = 0.0221; DESeq2), Citrobacter (+10.44; padj = 0.0124; DESeq2), and Ruminococcus gnavus (+2.69; q < 0.0001; ANCOM–BC) were more abundant in the CMIAP group. Conclusions: Infants with CMIAP exhibit gut dysbiosis, which is characterised by the depletion of beneficial commensals and the enrichment of potential pathogens, independent of maternal dairy intake. Further studies should establish whether these microbiota alterations are causal or consequential in CMIAP. Full article

Background: The pathophysiology of non-IgE-mediated cow’s milk allergy is mostly unknown. Previous studies suggested a mechanism mediated by T cells, but this was not confirmed in subsequent studies. The aim of this study was to investigate the immunological mechanisms, especially the role of regulatory T cells (Tregs), in the pathophysiology of allergic proctocolitis (FPIAP). Methods: A prospective observational study was conducted on infants with FPIAP and a control group of healthy infants with similar ages. The main variables were lymphocyte populations, included Tregs, which were extracted from peripheral blood and processed immediately by flow cytometry at two time points: in the acute phase (“T0”) and after clinical resolution (“Tres”). Results: A total of 32 patients with FPIAP and 10 healthy infants were enrolled. There was a higher T-CD4 memory cell count, increased numbers of regulatory B cells and a higher percentage of Tregs (p < 0.01) in patients with acute FPIAP in contrast to the healthy group. The levels of granulocytes (mainly eosinophils), dendritic cells (mDC2) and NK16+56- cells were also significantly higher in the FPIAP group. NK16+56- cells and the number of granulocytes appeared to be the best markers for distinguishing between the healthy and FPIAP infants based on the ROC curves. Conclusions: FPIAP does not appear to have an immune mechanism mediated by T cells, but it may be associated with innate immunity responses characterized by an increase in NK16+56- cells, eosinophils and dendritic cells. These cells could be evaluated in future studies as possible markers of non-IgE-mediated cow’s milk protein allergy. Full article

Background/Objectives: Pediatric patients with non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) may experience alterations of nutritional status. This non-randomized, prospective intervention study investigated the impact of dietary counseling on nutritional status in pediatric patients with non-IgE-GIFAs. Methods: Patients of both sexes aged 0–14 years newly diagnosed with non-IgE-GIFAs received dietary counseling provided by certified pediatric dietitians immediately after diagnosis. Nutritional status parameters were assessed to identify nutritional status alterations at baseline and after 12 months of intervention (T12). Results: The study included 100 patients (58% male, mean age 8.5 ± 8.8 months). Non-IgE-GIFAs phenotypes included food protein-induced enteropathy (FPE, 44%), food protein-induced enterocolitis syndrome (FPIES, 11%), food protein-induced allergic proctocolitis (FPIAP, 17%), and food protein-induced motility disorders (FPIMD, 28%). At diagnosis, 1% was affected by obesity (1 FPIAP), 5% were affected by overweight (2 FPE, 1 FPIAP, and 2 FPIMD), 7% were moderately underweight (5 FPE and 2 FPIMD), 1% was severely underweight (1 FPE), 7% were moderately stunted (4 FPE, 1 FPIAP, and 2 FPIMD), 16% were moderately wasted (11 FPE, 1 FPIES, 1 FPIAP, and 3 FPIMD), and 4% were severely wasted (2 FPE and 2 FPIMD). At T12, improvements in anthropometric parameters were observed, along with a reduction in the prevalence of malnutrition by excess (6% at diagnosis vs. 2% at T12) and a reduction in the undernutrition subtypes rate, including underweight, stunting, and wasting (26% at diagnosis vs. 3% at T12, p < 0.001). Conclusions: Non-IgE-GIFAs can negatively impact the nutritional status of pediatric patients. Thus, dietary counseling could be an effective strategy for preventing and managing nutritional alterations in these patients. Full article

Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated food allergy, usually presenting as bloody stools in breastfed, well-appearing, and regularly growing infants. The aim of our study was to describe the clinical features of Italian infants affected by FPIAP and their management and natural history in a real-life setting. Methods: A retrospective, observational study was performed at two tertiary pediatric hospitals (Florence and Trieste), including FPIAP-diagnosed infants between 2012 and 2022. Results: Most of the 100 enrolled patients were breastfed (68.0%), and the majority of those who underwent diagnostic tests (n = 51) showed normal hemoglobin and total IgE levels. A maternal elimination diet was performed in 69.0%, mostly for milk only, but 40.6% underwent multiple elimination diets. The remission rate was high both in breastfed infants (76.8%) and in those who received extensively hydrolyzed formula (81.8%). Nine subjects were left on a free diet, but six were lost at follow-up. The median time of complete remission was 30 days (IQR 14–60). Culprit food reintroduction was tolerated at a median age of 8 months (IQR 6–11), in ladder modality (for hen’s egg and cow’s milk) in 61.7%. Nine patients relapsed (14.3%) upon reintroduction with no associated variables identified at the regression analysis. The relapse rate was slightly higher when trigger food reintroduction was attempted > 12 months (16.7%) versus <12 months (13.0%). Conclusions: In our population, FPIAP had, as expected, a benign evolution. The early reintroduction of the suspect food in a gradual manner for cow’s milk and hen’s egg leads to good tolerance within the first year in most patients, avoiding unnecessary elimination diets. Full article

Background: Stunting is a common issue affecting children who suffer from chronic malnutrition in Indonesia. The Indonesian government has introduced supplementary food programs for stunted children, but the results have been less satisfactory. This may be due to the presence of anaemia and comorbid diseases. Haematology tests and inflammation markers are necessary to identify these conditions. This study aimed to examine the anaemia profiles and inflammation markers in stunted children under two years old. Methods: A cross-sectional descriptive design with cluster samples and consecutive analysis was used. The study was conducted between December 2023 and March 2024 at the West Nusa Tenggara Hospital and Palabuhanratu Sukabumi Hospital laboratories. Samples were obtained from various Public Health Centres in Sukabumi, West Java, North Maluku, and West Nusa Tenggara. Data collection comprised interviews, measurements, and the assessment of haematology, biochemical, and inflammatory markers. Statistical analysis was conducted using SPSS version 20, which includes descriptive analysis, correlation, comparison, and chi-square tests. Results: Two hundred and ten stunted children were identified with various anaemias and comorbidities. These anaemias included suspected thalassemia (38.1%), iron deficiency (18.1%), and anaemia of chronic diseases (13.3%). Based on the inflammatory markers obtained, TB was suspected (21.4%), inflammatory bowel disease (18.1%) was suspected, and allergic proctocolitis was suspected (31.9%). Conclusions: Analysis of the anaemia profiles and inflammatory markers revealed various types of anaemia and suspected comorbidities in stunted children. It is recommended that anaemia profiles and inflammation markers be assessed at the primary healthcare level. Full article

The bloody stools of newborns may be a clue for several clinical entities of varying severity, ranging from idiopathic neonatal transient colitis to food-protein-induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). Distinguishing among them at an early stage is challenging but crucial, as the treatments and prognoses are different. We conducted a monocentric retrospective study including all pre-term infants with bloody stools admitted to the Neonatal Intensive Care Unit (NICU) of the Vittore Buzzi Children’s Hospital (Milan) from December 2022 to May 2024. Patients diagnosed with NEC exhibited significantly lower eosinophil counts and higher procalcitonin levels than both patients with FPIAP and patients with idiopathic neonatal transient colitis, as well as a statistically significant increase in pathological features from abdomen ultrasounds and abdominal X-rays. In contrast, no lab markers or imaging techniques have been demonstrated to be useful in distinguishing between idiopathic neonatal transient colitis and FPIAP. Thus, after excluding a diagnosis of NEC, the only way to confirm FPIAP is through the oral food challenge, which can be performed in premature newborns presenting with bloody stools who are otherwise healthy and under medical supervision, in order to identify infants who may benefit from a cow’s-milk-free diet. Full article

Objective: The aim of our study was to investigate whether a 1-month-long milk-free diet results in a reduction in faecal calprotectin (FC) and faecal-zonulin-related proteins (FZRP) in children with milk-protein-induced allergic proctocolitis (MPIAP). Materials and methods: This is a single-centre, prospective, observational cohort study involving 86 infants with MPIAP, aged 1–3 months, and 30 healthy controls of the same age. The FC and FZRP were marked using the ELISA method (IDK^® Calprotectin or Zonulin ELISA Kit, Immunodiagnostik AG, Bensheim, Germany). The diagnosis of MPIAP was confirmed with an open milk challenge test. Results: FFC and FZRP proved useful in evaluating MPIAP treatment with a milk-free diet, and the resolution of allergic symptoms and a significant (p = 0.0000) decrease in the concentrations of both biomarkers were observed after 4 weeks on the diet. The FC and FZRP concentrations were still higher than in the control group. A high variability of FC concentrations was found in all the study groups. An important limitation is the phenomenon of FZRP not being produced in all individuals, affecting one in five infants. Conclusions: FC and FZRP can be used to monitor the resolution of colitis in infants with MPIAP treated with a milk-free diet, indicating a slower resolution of allergic inflammation than of allergic symptoms. The diagnosis of MPIAP on the basis of FC concentrations is subject to considerable error, due to the high individual variability of this indicator. FZRP is a better parameter, but this needs further research, as these are the first determinations in infants with MPIAP. Full article

Non-IgE immune-mediated gastrointestinal disorders constitute a heterogeneous group of enigmatic conditions that are on the rise. This category encompasses entities like food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). These are immune-mediated reactions to certain foods without the involvement of allergen-specific IgE in their pathogenesis. Eosinophilic esophagitis (EoE) is also included in this group, acknowledged for its mixed IgE and non-IgE-mediated characteristics. The diagnostic landscape is fraught with challenges, given the poorly understood nature of these disorders and their propensity to manifest with varying and overlapping clinical presentations, typically emerging in infancy with common potential triggers such as cow’s milk and soy. Presently, confirmatory testing for most of these conditions is limited and invasive, emphasizing the pivotal role of a thorough history and physical examination in reaching a diagnosis. Notably, there are limited guidelines for diagnosis and management for most of these disorders. This article elucidates the key distinctions among these disorders, provides an overview of existing diagnostic and therapeutic approaches, and addresses existing knowledge and research gaps. The considerable impact on the quality of life of non-IgE immune-mediated allergic disorders of the gastrointestinal tract, which can result in debilitating complications such as nutritional deficiencies, mental health disorders, and eating disorders, underscores the urgency for comprehensive exploration and management strategies. Full article

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. Full article

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. Full article