Purpose of the Study
To investigate the natural history of cow milk protein intolerance (CMPI) in infants.
Twelve infants (6 boys and 6 girls) with persistent CMPI were followed from birth until a median age of 5 years. Controls were 26 children (12 boys, 14 girls), median age 6 years, with CMPI that resolved within 1 to 2 years.
A retrospective chart review of patients with CMPI followed over a period of 7 years. Clinical suspicion of CMPI was confirmed by a double-blinded, placebo-controlled, food challenge (DBPCFC), within 4 to 6 weeks after onset of symptoms, after the patients had followed a CMP-free diet. The immunologic status of the study subjects was evaluated at baseline, including total serum immunoglobulin E, IgG anti-β-lactoglobulin, and radioallergosorbent tests (RASTs) for whole cow milk, β-lactoglobulin, α-lactoalbumin, and casein. At the end of the study these tests were repeated, and in addition RASTs and skin tests were performed for other foods and environmental allergens.
Family history of allergic disease was significantly more frequent in patients (11/12) than in the controls (10/26), p < .01. In all the studied subjects symptoms regressed during CMP-free diet. Clinical reactions to CMP challenge after 9–12 months of CMP-free diet in 5/12 patients with persistent CMPI were different than the ones present at diagnosis. There was an increase in respiratory reactions (wheezing), which occurred in 6/12 patients, compared with 1/12 at the initial diagnosis, and there was a growing tendency to reactions being delayed. At diagnosis only 2/12 patients had delayed reaction, while at the final challenge 9/12 had reactions that occurred >48 hours after the challenge. At diagnosis 5/12 patients with persistent CMPI had a positive RAST to CM antigens, compared with 6/26 controls. At the end of the study there was no increase in frequency of positive RASTs in patients with persistent CMPI but there were no controls with positive RASTs to CM antigens. A total of 11/12 patients with persistent CMPI showed intolerance to other foods (egg-10, tomato-3, banana-3, orange-2, chicken-2, cocoa-1) confirmed by DBPCFC. In the controls the frequency of multiple food intolerance was 3/26 (soy-2, egg-1). During the study other atopic disease was frequently observed in children with persistent CMPI: asthma (8/12), rhinitis (1/12), eczema (1/12). In controls only 2/26 infants showed other atopic disease.
Persistent CMPI forms are characterized by considerable importance of familial atopic disease, change in CMPI manifestations over time, more prolonged delay between CMP consumption and manifestation of symptoms, and very high frequency of multiple food intolerance and atopic disease.
Some authors indicate that CMPI symptoms regress within 3 years in majority of patients, while others find that 33% to 44% of infants are still intolerant at 4 years of age. This study confirms that infants with CMPI are a heterogeneous group of patients. In this study approximately 2/3 of infants outgrew their intolerance within 12 months after institution of strict CMP elimination diet. These infants in general did not have the tendency towards other forms of allergic disease, which may suggest that in their case CMPI was a manifestation of gastrointestinal tract immaturity. However, one third of infants had persistent CMPI at 5 years of age despite strict avoidance. They also frequently developed other food, respiratory, or skin allergic disease. It appears that in this subset of patients with positive family history, food allergy is the first manifestation of atopy. These patients should be followed closely with careful introduction of new foods and monitoring for the development of new food and environmental allergies.