Delayed reaction to cow's milk proteins: a case study

Allergy to cow's milk proteins has been defined as any adverse reaction mediated by immunological mechanisms to one or several of these proteins. The diagnosis can be made based on clinical manifestations supported by immune activation of in vitro parameters. Reactions to cow's milk have been classified according on their onset as immediate (< 45 min) or delayed-type (from 2 h to days). We describe a patient with late respiratory manifestations after milk intake, probably due to more than one immunological mechanism. He was an 18-year-old male who since infancy had presented serous rhinorrea, sneezing, nasal blockade, oropharyngeal pruritus and occasional dyspnea 12 to 48 h after ingestion of milk and its derivates. We performed skin prick and intradermal tests with whole milk and fractions. Patch tests were also carried out with whole milk purchased at a supermarket and with the extracts described, in their original form and vehiculized in vaseline. Total and serum specific IgE and IgG4 to milk fractions, histamine release test (HRT) to milk fractions, and precipitating antibodies by contraimmunoelectrophoresis against milk fractions were also measured. As a control we repeated this test in a patient with IgE-mediated manifestations to milk proteins and in two healthy controls. We performed a single-blind placebo controlled challenge with whole milk. Skin prick and intradermal tests were negative. Patch test (48 h) was positive for whole milk and whole milk vehiculized in vaseline, and for alpha-lactalbumin. Total IgE was 559 kU/l; serum-specific IgE was negative; IgG4 was positive (9.48% for alpha-lactalbumin; 7.41% for beta-lactoglobulin and 9.85% for casein). HRT was positive for casein (34%). We found precipitating antibodies to the three milk fractions in our patient and in the atopic control. In the challenge test, 10 h after milk intake the patient presented serous rhinorrea, sneezing and nasal blockade. IgG4 was involved as a blocking or anaphylactic antibody and as an immunological epiphenomenon reflecting a permanent antigenic stimulus. We find this last explanation to be the most coherent in this case.