Evaluation of the development of functional gastrointestinal diseases in children between 4-18 years old with cow's milk protein allergy

Background: Cow's milk protein allergy (CMPA) is one of the most common food allergies that occurs in early childhood. It is thought that CMPA may play a role in the pathophysiology of functional gastrointestinal diseases (FGİD) in the long term. In this study, our aim is to question the gastrointestinal symptoms in the long-term follow-up of patients with CMPA diagnosis, to recognize and gain awareness of frequently encountered FGİD, and to compare the development of FGİD in IgE and non-IgE (non-IgE mediated) CMPA patients. Materials and Methods: Our study includes patients diagnosed with CMPA, whose treatments were finalized and whose current ages were between 4 and 18, who applied to General Pediatrics, Pediatric Gastroenterology and Pediatric Allergy and Immunology Polyclinics between January 01, 2011 and December 30, 2019. The control group consisted of 250 healthy children of similar age group who were not diagnosed with CMPA. The patients were administered the Pediatric Gastrointestinal Symptoms Questionnaire including Rome IV criteria. Laboratory findings of the children (skin prick test, total IgE, complete blood count) were obtained from patient files and hospital system records. Results: In our study, the mean age of the CMPA patient group was 5.6 ± 2.0 (age±SD) years, and the mean age of patients without CMPA was 6.5 ± 3.1 (age±SD) years. Presenting symptoms were diarrhea (46.8%), frothy mucous stool (26.4%), atopic dermatitis (22.8%), bloody stool (19.6%), constipation (5.2%), colic (1.6%), wheezing (1.2%), and angioedema (1.2%). The most common additional allergic diseases were asthma (2.8%), atopic dermatitis (0.8%), and allergic rhinitis (0.4%). Eosinophilia was present in 79 (31.6%) patients, milk-specific IgE positivity was present in 98 (39.2%) patients, and skin prick test positivity was present in 64 (25.6%) patients. 107 (42.8%) of the patients were diagnosed with IgE-mediated CMPA. Functional GIS disease was observed in 70 (28%) of the patients with CMPA and in 76 (30.4%) of those without CMPA (p=0.623). FGID was observed in 36 (33.6%) patients with IgE-mediated CMPA and in 34 (23.8%) patients with non-IgE-mediated CMPA. Functional abdominal pain, irritable bowel syndrome and encopresis were significantly more common in patients without CMPA (p=0.009, p=0.016, p=0.01, respectively). Functional constipation was observed more frequently in patients with CMPA and was found to be statistically significant (p=<0.001). Functional dyspepsia, functional abdominal pain and irritable bowel syndrome were observed more frequently in patients with IgE-mediated CMPA (p=<0.001, p=0.001, p=0.002, respectively). Functional constipation was observed more frequently in patients with non-IgE-mediated CMPA (p=0.018). Conclusion: Although the frequency of FGID development does not increase significantly in the long term in patients diagnosed with CMPA, functional dyspepsia, functional abdominal pain, and irritable bowel syndrome are considerably higher, especially in those with IgE-mediated ones. It appears that the development of FGID has multifactorial causes, and especially IgE-mediated CMPA may be an important risk factor for these diseases. Keywords: Functional gastrointestinal disease, Cow's milk protein allergy, , Rome IV criteria