Guideline sources The following summarized guidelines for the evaluation and management of milk protein allergy (MPA) are prepared by our editorial team based on guidelines from the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHN 2022), the British Society for Allergy and Clinical Immunology (BSACI 2014), the American Academy of Allergy, Asthma & Immunology (AAAAI/ACAAI 2014), the European Academy of Allergy and Clinical Immunology (EAACI 2014), and the National Institute of Allergy and Infectious Diseases (NIAID 2010). 1 2 3 4 5 Guidelines 1. Screening and diagnosis Clinical presentation: As per LASPGHN 2022 guidelines, recognize that: symptoms of IgE-mediated cow's MPA are diverse and involve a variety of organs and systems https://web.pathway.md/diseases/recsneKR575tpLVN3 1/5 6/30/23, 1:02 AM Milk protein allergy Pathway 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. B As per BSACI 2014 guidelines, recognize that: the prevalence of cow's milk allergy is 1.8-7.5% of infants during the first year of life B cow's milk allergy commonly presents in infancy with most affected children presenting with symptoms by 6 months of age and onset is rare after 12 months B cow's milk allergy has a favorable prognosis, as most children will outgrow their allergy by adulthood B 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 B cow's milk allergy in adults more commonly arises in adulthood but may persist from childhood, and is frequently a severe form of allergy where up to 25% have experienced anaphylaxis. B Diagnosis: As per LASPGHN 2022 guidelines, establish the diagnosis of cow's MPA clinically and do not obtain laboratory tests for its corroboration. B As per BSACI 2014 guidelines, establish the clinical diagnosis of IgE-mediated disease by a combination of typically presenting symptoms, such as urticaria and/or angioedema with vomiting and/or wheeze, soon after ingestion of cow's milk and evidence of sensitization (presence of specific IgE), recognizing that the spectrum of clinical severity ranges from skin symptoms only to life-threatening anaphylaxis. B Show 4 more 2. Diagnostic investigations Skin prick test: As per LASPGHN 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. C https://web.pathway.md/diseases/recsneKR575tpLVN3 2/5 6/30/23, 1:02 AM Milk protein allergy Pathway Do not obtain skin prick tests or specific IgE blood tests for diagnostic confirmation of cow's MPA in pediatric patients. D As per BSACI 2014 guidelines, view a skin prick test weal size 5 mm ( 2 mm in younger infants) as strongly predictive of cow's MPA. B Oral food challenge: As per LASPGHN 2022 guidelines, consider conducting an open oral food challenge to confirm the diagnosis of cow's MPA and characterize the development of oral tolerance, especially in infants. C Show 6 more As per BSACI 2014 guidelines: Consider conducting a food challenge to confirm the diagnosis of IgE-mediated disease if there is a conflict between the history and diagnostic tests. C Conduct food elimination and reintroduction for the assessment of non-IgE-mediated cow's milk allergy if there is diagnostic uncertainty. B Other tests: As per LASPGHN 2022 guidelines, do not obtain specific IgG, patch testing, complementary laboratory tests, or gastrointestinal endoscopy for diagnostic confirmation of IgE-mediated or non-IgE-mediated cow's MPA. D As per BSACI 2014 guidelines, recognize that the reported level of IgE required to support a diagnosis of IgE-mediated cow's milk allergy varies between studies and depends on the research population. B 3. Nonpharmacologic interventions Elimination diet: As per LASPGHN 2022 guidelines, offer an elimination diet excluding allergenic proteins for controlling the clinical manifestations of cow's MPA. B Show 8 more As per BSACI 2014 guidelines: Eliminate cow's milk and cow's milk products and substitute with an allergenically and nutritionally suitable milk alternative for the management of cow's milk allergy. B Take into account the age of the child, the severity of the allergy, and the nutritional composition of the substitute when choosing cow's milk substitute as nutritionally incomplete substitutes can lead to faltering growth and specific nutritional deficiencies. B As per EAACI 2014 guidelines: Offer extensively hydrolyzed, hypoallergenic cow's milk formulas as the first choice for the treatment of cow's milk allergy, especially in infants and young children. Consider offering amino acid formulas, especially for the subgroup of patients with more severe symptoms. A https://web.pathway.md/diseases/recsneKR575tpLVN3 3/5 6/30/23, 1:02 AM Milk protein allergy Pathway Do not use soy formulas before 6 months of age and at any age in the presence of gastrointestinal symptoms. Consider offering in patients at 6-12 months of age on a case-by- case basis. D 4. Patient education Nutritional counseling: As per AAAAI 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. B Show 2 more As per BSACI 2014 guidelines, assess calcium intake and initiate dietary or pharmaceutical supplementation, if appropriate, by a dietitian as cow's milk is the major source of calcium in infant diets and children on milk exclusion diets are at risk of a deficient calcium intake. B As per NIAID 2010 guidelines, provide nutritional counseling and obtain regular growth monitoring in all pediatric patients with food allergies. B 5. Preventative measures Primary prevention: consider offering a partially or extensively hydrolyzed infant formula, if exclusive breastfeeding is not possible, for possible prevention of cow's MPA in infants with a family history of atopy. C 6. Follow-up and surveillance Follow-up: As per LASPGHN 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. C Show 2 more As per BSACI 2014 guidelines: Reassess patients at 6-12 monthly intervals from 12 months of age to assess for suitability of reintroduction as cow's milk allergy will resolve in the majority of children. B Consider reintroducing cow's milk graded according to the 'milk ladder' with less allergenic forms offered initially and more allergenic forms then eaten sequentially as tolerated. Consider reintroducing at home or supervised in the hospital. C Clinical findings Symptoms Past medical history https://web.pathway.md/diseases/recsneKR575tpLVN3 4/5 6/30/23, 1:02 AM Milk protein allergy Pathway Abdominal cramps Allergic rhinitis Constipation Allergy Diarrhea Asthma Dysphagia Atopic dermatitis Itching Atopy Lightheadedness Respiratory exam No history of cough Rhinorrhea Stridor Skin flushing Wheezing Syncope Serological findings Vomiting milk protein-specific IgE Vital signs Hypotension Tachycardia Integument exam Diaphoresis Urticaria References 1. D Luyt, H Ball, N Makwana et al. BSACI guideline for the diagnosis and management of cow's milk allergy. Clin Exp Allergy. 2014;44 5 642 72. Open 2. M C Toca, M B Morais, R V zquez-Frias et al. Consensus on the diagnosis and treatment of cow's milk protein allergy of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Rev Gastroenterol Mex Engl Ed). 2022 May 24;S2255 534X 22 00033 0. Open 3. NIAID Sponsored Expert Panel, Joshua A Boyce, Amal Assa'ad et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010 Dec;126 6 Suppl):S1 58. Open 4. Hugh A Sampson, Seema Aceves, S Allan Bock et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol. 2014 Nov;134 5 1016 25.e43. Open 5. Muraro A, Werfel T, Hoffmann-Sommergruber K et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy. 2014 Aug;69 8 1008 25. Open https://web.pathway.md/diseases/recsneKR575tpLVN3 5/5