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Milk protein allergy

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Updated 2024 WAO guidelines on the use of milk formulas in infants with cow's milk allergy.

Background

Overview

Definition
MPA is an adverse immune reaction to one or more of the proteins found in milk, most commonly cow's milk, which are normally harmless to a non-allergic individual.
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Pathophysiology
The pathophysiology of MPA involves an aberrant immune-mediated reaction against milk proteins, with or without involvement of IgE.
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Epidemiology
The incidence of MPA is estimated at 2-7.5% in the first year of life, with a lower rate in breastfed infants.
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Disease course
The clinical course of MPA can vary, but common symptoms include gastrointestinal symptoms, skin reactions, and respiratory problems. In IgE-mediated disease, symptoms such as urticaria, angioedema, vomiting, wheezing, and anaphylaxis occur soon after ingestion of cow's milk, and there is evidence of sensitization (presence of specific IgE). Non-IgE-mediated cow's milk allergy presents with delayed onset of predominantly gastrointestinal symptoms, including proctocolitis, enteropathy, and cow's milk proteins-induced food protein-induced enterocolitis syndrome, or with symptoms resembling functional gastrointestinal disorders, such as infant colic, infant regurgitation, and constipation. In non-IgE-mediated disease, gastrointestinal and cutaneous symptoms improve or resolve with exclusion and reappearing with reintroduction of cow's milk.
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Prognosis and risk of recurrence
The prognosis for MPA is generally good, with most children outgrowing the allergy by adolescence. However, cow's milk allergy is more likely to persist in IgE-mediated disease and where there is greater sensitivity, multiple food allergies, and/or concomitant asthma and allergic rhinitis.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of milk protein allergy are prepared by our editorial team based on guidelines from the World Allergy Organization (WAO 2024), the American Academy of Family Physicians (AAFP 2023), the Global Allergy and Asthma European Network (GA²LEN 2022), the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN 2022), the European ...
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Screening and diagnosis

Clinical presentation: as per LASPGHAN 2022 guidelines, recognize that:
symptoms of IgE-mediated cow's MPA are diverse and involve a variety of organs and systems
the skin and mucosa are more frequently affected, whereas gastrointestinal and respiratory tract symptoms are less common
cow's MPA in infants caused by mixed mechanisms (IgE-mediated and non-IgE-mediated) presents with skin-related symptoms, atopic dermatitis, and more rarely eosinophilic esophagitis
non-IgE-mediated cow's MPA clinically presents with the delayed onset of predominantly digestive symptoms, including proctocolitis, enteropathy, and cow's milk proteins-induced food protein-induced enterocolitis syndrome, or with symptoms resembling functional gastrointestinal disorders, such as infant colic, infant regurgitation, and constipation
the most frequent clinical presentation of cow's MPA in exclusively breastfed children is non-IgE-mediated proctocolitis, with little or no general involvement, and with good recovery after cow's milk protein is suspended from the diet of the mother and from the diet of the infant, at one year of age.
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  • Diagnosis

Diagnostic investigations

Specific allergy testing: as per LASPGHAN 2022 guidelines, consider obtaining skin prick tests and specific IgE blood tests only in patients with clinical symptoms consistent with IgE-mediated cow's MPA or in pediatric patients with a positive oral food challenge.
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Medical management

Immunotherapy: as per GA²LEN 2022 guidelines, consider offering oral immunotherapy under specialist supervision with standardized, evidence-based protocols using food products to increase the amount of allergen tolerated while on therapy in selected pediatric patients (aged > 4 years) with clinically diagnosed persistent severe IgE-mediated cow's milk allergy.
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Nonpharmacologic interventions

Elimination diet: as per LASPGHAN 2022 guidelines, offer an elimination diet excluding allergenic proteins for controlling the clinical manifestations of cow's MPA.
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  • Hydrolyzed infant formulas

Patient education

Nutritional counseling: as per AAAAI/ACAAI 2014 guidelines, advise patients allergic to certain specific foods about the risk of ingestion of similar cross-reacting foods, such as other mammalian milk in patients with cow's milk allergy.
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Preventative measures

Early introduction of cow's milk: as per AAFP 2023 guidelines, introduce cow's milk early at 4-6 months of age to reduce the risk of developing cow's milk allergy.
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Follow-up and surveillance

Follow-up: as per LASPGHAN 2022 guidelines, consider conducting an oral food challenge test at home after at least 6 months of treatment and/or having reached 1 year of age to confirm tolerance recovery for the non-IgE-mediated forms of cow's MPA.
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