Cow’s milk allergy (CMA) affects 2% to 3% of young children and presents with a wide range of IgE and non-IgE–mediated clinical syndromes, which have a significant economic and lifestyle effect. It is logical that a review of CMA would be linked to a review of soy allergy because soy formula is often an alternative source of nutrition for infants who do not tolerate cow’s milk. This review examines the epidemiology, pathogenesis, clinical features, natural history, and diagnosis of cow’s milk and soy allergy. Cross-reactivity and management of milk allergy are also discussed.
Epidemiology
General population birth cohorts report a prevalence of cow’s milk allergy (CMA) of 2.2% to 2.8% at 1 year of age, similar to the rate found in another large cohort followed for 18 to 34 months. Of those with CMA, about 60% have IgE-mediated CMA. A recent study from Israel by Katz and colleagues reported a much lower rate of CMA in infants (0.5%) than in 3-year-old children (0.6%). The investigators also reported a rate of 0.5% for non-IgE–mediated CMA in infants, equivalent to the rate of IgE-mediated CMA in infants. Childhood CMA is more prevalent in boys than girls. Regarding severe allergic reactions, cow’s milk (CM) comprises 10% to 19% of food-induced anaphylaxis cases seen both in the field and in emergency departments in pediatric and mixed-age populations. CM is the third most common food product to cause anaphylaxis, following peanut and tree nuts.
In general, soy allergy is not as common as CMA, even in atopic children. Bruno and colleagues found a prevalence of 1.2% in a cohort of 505 children suffering from allergic diseases and 0.4% in 243 children who had been fed soy protein formula in the first 6 months of life for supposed prevention of allergic diseases. In population-based studies, 2 European cohorts pointed to rates varying from 0.0% to 0.7% for children in double-blind placebo-controlled food challenge. Also, up to 10% to 14% of patients with CMA also present with soy protein allergy. In a study by Klemola and colleagues, adverse reactions to soy were seen more often in milk-allergic individuals younger than 6 months. In this study, at 2-year follow-up, sensitization to soy proteins was not higher in infants fed soy formula than in those fed extensively hydrolyzed formulas ( P = .082; n = 70). One recent study reported that of 66 infants with IgE-mediated CMA, none had a proven allergy to soy, with 64 of 66 tolerating soy in their diets.
Dietary exposure to milk, soy, and products containing either or both vary in different parts of the world. Traditional Asian cuisine includes less milk sources than the Western cuisine but includes several natural soy sources. Meanwhile, the consumption of soy-containing food additives (soy isolate, soy concentrate, and soy flour) is increasing in Western diets. This interesting geographic divergence may lead to a difference in the prevalence of soy and milk allergy between different populations, but this has not been confirmed.
Clinical manifestations
Patients with CMA and soy allergy present with a wide range of IgE-mediated and non-IgE–mediated clinical syndromes ( Table 1 ). IgE-mediated reactions occur immediately or within 1 to 2 hours of ingestion, whereas non-IgE–mediated reactions generally have a delayed onset beyond 2 hours of ingestion. Both humoral and/or cell-mediated mechanisms play a role in mixed manifestations, which may present with acute or chronic symptoms, making the causal relationship to foods more difficult to detect. Clinical symptoms of CMA commonly appear during the first months of life, usually within days or weeks after feeding with CM-based formulas have been started or may sometimes be seen in exclusively breast-fed infants. With such an early age of onset, symptoms of an erythematous rash or hives shortly after intake of CM (or infrequently soy) formula are suggestive of food allergy. The role of food allergy in causing flares of atopic dermatitis is less clear, although up to one-third of moderate to severe atopic dermatitis may in fact be because of CMA.
| IgE Mediated | |
|---|---|
| Cutaneous | Urticaria Angioedema |
| Gastrointestinal | Oral itching and abdominal pain Nausea and vomiting Diarrhea |
| Respiratory | Rhinoconjunctivitis Wheeze and asthma exacerbation Laryngeal edema |
| Systemic | Anaphylaxis |
| Mixed IgE mediated and non-IgE mediated | |
| Cutaneous | Atopic dermatitis |
| Gastrointestinal | Eosinophilic esophagitis and gastroenteritis |
| Non-IgE mediated | |
| Gastrointestinal | Dietary protein enterocolitis/proctitis/proctocolitis Protein-losing enteropathy GER a Colic a Constipation a |
| Respiratory | Pulmonary hemosiderosis (ie, Heiner syndrome; mostly caused by milk allergy) |
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