THE NATURAL-HISTORY OF COWS MILK PROTEIN ALLERGY INTOLERANCE

In prospective studies the incidence of cow's milk protein allergy and intolerance (CMPA/CMPI) in infancy in western industrialized countrie s has been estimated to be about 2-3% based on strict diagnostic crite ria. A significant association between early neonatal exposure to cow' s milk formula feeding and subsequent development of CMPA/CMPI has bee n documented, The small amounts of 'foreign' protein in human milk may rather induce tolerance than allergic sensitization. The findings of specific IgE to individual cow's milk proteins in cord blood of the ma jority of infants who later develop CMPA/CMPI suggests a prenatal sens itization may play a role in the pathogenesis of CMPA/CMPI. Perhaps a weak intrauterine eduction of low IgE-response may need to 'boosted' n eonatally in order to cause clinical disease. The prognosis of CMPA/CM PI is good with a recovery of about 45-56% at one year, 60-77% at two years and 71-87% at three years. Associated adverse reactions to other foods, especially egg, soy, peanut and citrus develop in about 41-54% . Allergy to potential environmental inhalant allergens has been repor ted in up to 28% by three years and up to 80% before the age of pubert y. Especially, infants with an early increased IgE response to cow's m ilk protein have an increased risk of persisting CMPA, development of persistent adverse reactions to other foods and development of allergy against environmental inhalant allergens. Cow's milk protein allergy/ intolerance (CMPA/CMPI), meaning reproducible adverse reactions to cow 's milk protein(s) may be due to the interaction between one or more m ilk proteins and one or more immune mechanisms, possibly any of the fo ur basic types of hypersensitivity reactions. Immunologically mediated reactions are defined as CMPA. Mostly, CMPA is caused by IgE-mediated (type I) reactions, but evidence for type III (immune complex) reacti ons and type IV (cell mediated reactions) have been demonstrated as re viewed by Host (1994) and Ortolani & Vighi (1995). Non immuno-logicall y reactions against cow's milk protein(s) are defined as CMPI. However , it should be stressed that many studies on 'cow's milk allergy' have not investigated the immunological basis of the clinical reactions. I n most instances of cow's milk protein hypersensitivity only diagnosti c investigations such as skin prick test and RAST indicative of IgE-me diated reactions are performed. In fact, CMPA cannot be ruled out unle ss extensive diagnostic tests for type II-III-IV reactions have proved negative. Thus, the classification of adverse reactions to cow's milk proteins depends on the extent and the quality of performed diagnosti c tests for immune mediated reactions. At present, no single laborator y test is diagnostic of CMPA/CMPI, and differentiation between CMPA an d CMPI cannot be based solely on clinical symptoms. Therefore the diag nosis has to be based on strict well-defined elimination and milk chal lenge procedure (Hill & Hosking, 1991), (Host, 1994). Preferably, doub le-blind placebo-controlled challenges (DBPCFC) should be carried out in children older than 1-2 years of age. In infants open controlled ch allenges have been shown to be reliable when performed under professio nal observation in a hospital setting (Host & Halken, 1990).