Development of allergic disorders in children with cow's milk protein allergy or intolerance in infancy

Adverse reactions to cow's milk, indicated as cow's milk protein allergy or intolerance (CMPA/CMPI), are one of the most common adverse reactions to foods in infancy and early childhood with an incidence ranging from 2% to 5%, when strict diagnostic criteria are used. In 1995, the European Academy of Allergy and Clinical Immunology proposed a classification of adverse reactions to foods based on mechanism. `Adverse reaction to food', like cow's milk, is defined as any aberant reaction following the ingestion of a food or food additive. Adverse reactions can be divided into toxic and nontoxic food reactions. A toxic reaction is an adverse reaction which will occur in every person provided that a sufficient dose has been taken in. Nontoxic reactions can be divided in immune-mediated mechanisms (allergy), and nonimmune-mediated mechanisms (intolerance), and the occurrence depends on the susceptibility of the person. Analogous, adverse reactions to cow's milk protein can be divided in CMPA and CMPI. CMPA can be classified according to the type of immune mechanisms, that is IgE-mediated (type I) reactions, and non-IgE-mediated reactions, as type II (cytotoxic), type III (immune complexes), and type IV (cell-mediated) reactions. The definition of CMPI leads to some confusion. CMPI is defined as reproducible adverse reactions to cow's milk which are not immunologically mediated, e.g. enzyme deficiencies, absorption defects, pharmacological reactions, or infectious reactions. However, the term CMPI is also used in cases in which the immunological aetiology of a reaction to cow's milk protein is not confirmed, either due to a lack of immunological investigations, or negative results of the performed analyses. Therefore, the classification of adverse reactions to cow's milk proteins depends on the extensiveness, and the quality of the diagnostic tests that are used to investigate the immunological mechanisms.