Internet Symposium on Food Allergens 4(1): 19-106 (2002) [PDF-file]

Allergen Data Collection - Update:
Cow's Milk  (Bos domesticus)
Authors in alphabetical order [contact information]
Robert H.
BESLER (Hamburg, Germany)
EIGENMANN (Genève, Switzerland)
SCHWARTZ (Rochester, NY, USA)


Cow's milk allergy (CMA) can be defined as any adverse reaction mediated by immunological mechanisms to cow's milk proteins. CMA can be divided in IgE-mediated reactions (IgE-CMA) and non-IgE-mediated reactions (non-IgE-CMA) which may involve other immunoglobulins, immune complexes and cell-mediated reactions. Patients with non-IgE-CMA and digestive symptoms can present with the following well defined clinical pictures: milk- induced enterocolitis, milk- induced proctitis, milk- induced enteropathy, or eosinophilic allergic gastro-enteritis. CMA should be differentiated from cow's milk intolerance (CMI) reactions due to lactase deficiency or other non immune mediated causes which are not subject of the present review. Most CMA has its onset in the first year of life, and becomes apparent at the time of weaning from breastfeeding.
Prevalences of CMA range from 1.6% to 2.8% in randomly selected children younger than 2 years of age (elimination / challenge proven). Oral tolerance is frequently acquired in about 50 to 90% of children with CMA within the first 6 years of life. However, severe CMA may persist into adulthood. The frequency of sensitization to cow's milk in adults has recently been estimated by RAST to be 0.7% and 1.2% in Scandinavian countries.

According to the onset of symptoms after milk ingestion CMA can be classified as immediate or delayed- type. The clinical picture can vary from mild to severe, involving the skin (eczema, hives, angioedema), gastrointestinal tract (oral pruritis, colic, vomiting, diarrhea, constipation), respiratory tract  (cough, stridor, wheezing), and cardiovascular system (anaphylactic shock).
No single laboratory test is diagnostic of CMA. Clinical manifestations supported by skin tests and in vitro parameters are valuable. The diagnosis is confirmed by well-defined elimination and subsequent challenge procedures. If there is evidence of anaphylaxis, challenge should be avoided. The inadvertent ingestion of small amounts of cow's milk allergens hidden in foods can result in severe life- threatening clinical reactions. Cow's milk allergens could be present in breast milk, infant formulas, milk and milk products like cheese and yogurt, as well as in "non-dairy" foods occurring as contaminants or unlabeled additives. The most effective treatment of CMA is allergen avoidance. Besides the optimal choice of breast milk, suitable milk substitutes in the nutrition of infants with CMA are soy hydrolyzed formulas, extensively casein and whey hydrolyzed formulas, and amino acid formulas. The exact frequency of sensitization to soy protein in children with CMA is still controversial. Soy allergy seems to be rare in IgE-CMA, while approximately 60% of children with milk- induced enterocolitis are sensitive to soybean. However, severe anaphylactic reactions to extensively hydrolyzed casein and partially hydrolyzed whey formulas can occur in highly sensitized infants with IgE-mediated cow’s milk allergy. Due to the high homology of protein composition sheep's and goat's milk are cross-reactive in approximately 80% of subjects with CMA while mare's milk is only rarely cross-reactive with cow's milk (4% in subjects with CMA). In addition, sheep’s milk may cause severe IgE-mediated allergic reactions in children not affected by CMA. IgE antibodies from children allergic to cow’s milk are capable of recognizing milk proteins from mammals bred in European countries (ewe, goat, buffalo). Cross-reactivity of camel’s milk proteins has not been recognized. Therefore, due to clinically important residual allergenicity in some hypoallergenic formulas and milk allergen cross-reactivity between species, clinical testing in a safe medically-supervised environment is necessary in each cow’s milk sensitive infant before use.

In infants and children the major cow's milk allergens are casein (CAS), beta- lactoglobulin (beta-LG), and alpha- lactalbumin (alpha-LA). Caseins (alpha-, beta-, kappa-CAS) are the most important in children and adults. Other allergens involved in CMA are bovine serum albumin (BSA) and bovine immunoglobulins. Several IgE- binding epitopes of alpha-LA, beta-LG, alpha- and beta-CAS have been described. Knowledge of the immunodominant epitopes of the major allergens may be useful in identifying children who will have persistent CMA and children who are likely to outgrow CMA.
The present data collection summarizes the following topics in tabular form: prevalences of CMA, diagnostic and therapeutic features, molecular biological and allergenic properties of cow's milk allergens, stability and hidden presence of allergens, the use of infant formulas in therapy and prevention of CMA and other atopic diseases.
1 Prevalence of Cow's Milk Allergy
2 Outgrowing of Cow's Milk Allergy
3 Symptoms of Cow's Milk Allergy
4 Diagnostic Features of Cow's Milk Allergy
5 Therapy of Cow's Milk Allergy
6 Composition of Cow's Milk
7 Allergens of Cow's Milk
7.1 Sensitization to Cow's Milk
7.2 Properties of alpha-Lactalbumin
7.3 Properties of beta-Lactoglobulin
7.4 Properties of Bovine Serum Albumin
7.5 Properties of Caseins
8 Isolation & Preparation
9 Cross-Reactivities
10 Stability of Cow's Milk Allergens
11 Allergen Sources
12 Food Allergen Labeling
13 Infant Formulas
14 References

The reference lists of the Allergen Data Collections are based mainly on searches of Medline and FSTA (Food Science & Technology Abstracts) databases up to the related dates of publication. The scientific rigor of the studies listed is variable and not subject of critique or evaluation by the authors or the editor of the Allergen Data Collections. The reader should be aware of considerable problems in comparing data from different studies (eg. patient cohorts, diagnostic performances, possible flaws in allergen preparations and methodologies for allergen characterization) and is encouraged to review the original publications.
The information provided by the Internet Symposium on Food Allergens is for educational, communication and information purposes only and is not intended to replace or constitute medical advice or treatments. Neither the authors nor the editorial board of the Internet Symposium on Food Allergens is responsible for the use which might be made of the information.

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