Cow's milk protein allergy in infants and children

Cow's milk protein allergy (CMPA) is an immune-mediated reaction to cow's milk proteins, which can involve multiple organ systems including the gastrointestinal tract. Immunoglobulin E (IgE)-mediated response results in rapid onset of allergic symptoms that are easily recognizable. However, delayed (i.e., non-IgE/cell-mediated) or mixed (IgE- and cell-mediated) reactions produce a host of symptoms that overlap with other conditions and vary widely in onset and severity. Determining whether symptoms represent immune-mediated CMPA, non-immunologic reaction to cow's milk, or are unrelated to cow's milk exposure is challenging yet essential for effective management. While the clinical presentation of non-IgE-mediated CMPA can vary, this condition is usually self-limited and resolves by 1 to 6 years of age. Food antigen-specific immunoglobulin G (IgG) panels that are not evidence-based should be avoided because they can lead to overdiagnosis of presumed food intolerances. Overdiagnosis of CMPA can result in overuse of extensively hydrolyzed formulas and have significant cost implications for families. This statement focuses on delayed non-IgE/cell-mediated CMPA and assists health care providers to distinguish between and identify varied reactions to cow's milk, discusses the role of diagnostic testing, and provides management recommendations based on best evidence.