Pathophysiology of Cow's Milk Protein Allergy and Food Protein-Induced Allergic Proctocolitis

Core Immunologic Mechanisms

The American Academy of Allergy, Asthma, and Immunology suggests that T cell-mediated inflammation is the postulated central mechanism in non-IgE-mediated cow's milk protein allergy, though this requires further validation according to international consensus guidelines 1, 2, 3
The inflammatory cascade involves infiltration of lymphocytes, plasma cells, and polymorphonuclear leukocytes into the intestinal mucosa, causing increased permeability 1
The European Academy of Allergy and Clinical Immunology notes that the resulting fluid shift into the gastrointestinal lumen explains the profuse vomiting and bloody diarrhea in affected patients 1, 2, 4

The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition states that colonoscopic findings in FPIAP reveal loss of vascular pattern, spontaneous and induced friability, and variable degrees of ulceration with spontaneous bleeding 1
Histology shows polymorphonuclear leukocytic infiltration of the lamina propria or glands, with occasional crypt abscesses and mucus depletion from rectal glands 1

The European Society for Pediatric Gastroenterology, Hepatology and Nutrition notes that small intestinal damage with variable degrees of villous atrophy has been documented in infants with CMPA, causing carbohydrate malabsorption and watery stools positive for reducing substances 1, 5
Upper endoscopy in chronic presentations reveals gastric edema, erythema, mucosal friability, and gastric antral erosions 1

The American Academy of Pediatrics suggests that the successful use of ondansetron to treat vomiting, abdominal pain, and lethargy during FPIES challenges implies neuroimmune mechanism involvement beyond simple intestinal inflammation 1, 2
Inflammatory mediators activate neural pathways contributing to the profuse vomiting characteristic of acute presentations 1, 2

The American College of Gastroenterology notes that acute presentations occur with intermittent food exposures, allowing the immune system to "reset" between exposures, leading to dramatic reactions upon re-exposure 7, 6
Chronic presentations develop with daily ingestion, causing ongoing low-grade inflammation manifesting as chronic diarrhea, vomiting, and failure to thrive 1, 2, 7