Cow's milk protein allergy (CMPA) is one of the most common allergic disorders seen in young children. It most commonly affects children in the first year of life.
Clinical Editor's comments (October 2017)
Dr Hayley Willacy recommends the recently released international Milk Allergy in primary care guideline. The guideline includes updated recommendations on presentation and recognition of cow’s milk allergy (CMA); diagnosis; management of mild-to-moderate confirmed non-IgE-mediated CMA within primary care; suspected severe non-IgE-mediated CMA and referral. A number of additional resources have been developed alongside the guideline to support parents and carers, including an initial factsheet for parents; a home reintroduction protocol to confirm diagnosis; a milk ladder and milk ladder recipes.
CMPA affects about 7% of formula-fed babies but only about 0.5% of exclusively breast-fed babies, who also tend to have milder reactions. Exclusive breast-feeding may also protect babies from developing an allergy to cow's milk protein after they are weaned.
There are a number of different proteins in cows milk: there are five protein components in each of the casein and whey fractions of milk. A child can be allergic to one or more components within either group.
CMPA is more likely in children who have other atopic conditions such as asthma, eczema or hay fever, or if close family members have those conditions. The presence of atopic eczema is a predictor for sensitisation to common food allergens. The earlier the eczema starts and the more severe it is, the higher the risk of food allergy.
If there are other food allergies, it is more likely that CMPA will persist into later childhood.
Some work has been done looking at the development of food allergies and whether this can be prevented by feeding infants at risk with hydrolysed formula. However, the results have so far not been clear[6, 7].
Allergic reactions can be immunoglobulin E (IgE)-mediated reactions or non-IgE-mediated reactions. Cow's milk proteins can cause reactions of either type or both together, which can make them difficult to diagnose.
IgE-mediated reactions trigger histamine release and occur within two hours of milk being consumed. They include skin reactions such as itching, erythema, urticaria and acute angio-oedema, most commonly of the face. There can be abdominal symptoms such as colicky pain, nausea, vomiting and diarrhoea. Respiratory symptoms can be upper or lower respiratory tract: nasal itching, sneezing, rhinorrhoea, congestion, cough, chest tightness or wheeze.
It is extremely rare for cow's milk to trigger an anaphylactic reaction. Antihistamines can be used to treat the symptoms. Allergic reactions may be more severe in people with asthma, particularly if the asthma is poorly controlled.
This type of allergy can be diagnosed with a skin prick test or a blood test (specific IgE, previously known as RAST). If this type of allergy is suspected, refer the child to a paediatrician who will arrange for the test to be done in hospital.
Non-IgE-mediated reactions occur hours or days after consuming milk. Skin reactions such as atopic eczema are common, as well as itching and erythema. Abdominal symptoms include colicky pain (including infantile colic), reflux, blood or mucus in stools, constipation or diarrhoea. There may be lower respiratory tract symptoms such as cough, wheeze, breathlessness or chest tightness.The child may be pale and tired, and growth may be faltering.
The best way to establish if cow's milk is causing these symptoms is to exclude it from the diet. There should be an improvement in symptoms within two weeks.
With such a wide range of symptoms that can be caused by CMPA, the differential diagnosis is extensive, and includes other food allergies, non-food allergies such as pollen, animal dander, other gastrointestinal disorders, pancreatic insufficiency such as in cystic fibrosis, and infections - eg urinary tract infection.
The management of CMPA generally consists of avoidance of the allergen. If CMPA is the cause of the symptoms then they should resolve within two weeks of stopping cow's milk.
If the child is formula-fed, they can be given extensively hydrolysed milk formula such as Nutramigen®, Aptamil Pepti® or Pepti Junior®. These are based on cow's milk but the proteins are broken down into smaller peptides that are less likely to trigger an allergic reaction.
Babies who have CMPA may have their growth and development impaired by the disorder; however, hydrolysed formula is shown to provide balanced nutrition and to restore normal growth and development[12, 13].
If the symptoms persist on hydrolysed formula but a suspicion of CMPA remains, then try an amino acid formula. These include Nutramigen AA® and Neocate LCP®. Hydrolysed milks are cheaper and are also generally better tolerated, although the flavour and tolerability varies.
If the child is breast-fed and the mother wishes to continue breast-feeding, she must eliminate milk and milk products from her diet. This will include checking ingredients for anything derived from milk, such as casein, whey and lactose. The mother should make sure she is still getting adequate calcium in her diet. It is recommended that she be offered calcium and vitamin D tablets; however, calcium can also come from tinned fish, pulses, almonds, kale, oranges and soya products such as soya milk and tofu.
Babies who are being weaned, and older children with persisting CMPA, will need to follow a cow's milk-free diet as above. Parents must be advised about how to check the ingredients of processed foods for milk-derived constituents. Children should be referred to a paediatric dietician for advice about maintaining a balanced diet while excluding allergens.
The prognosis of CMPA is good with a remission rate of approximately 45-50% at 1 year, 60-75% at 2 years and 85-90% at 3 years. Children can have a challenge test every 6-12 months to see if they are able to tolerate milk. It may take several days for the reaction to show, particularly for non-IgE allergy.
The challenge test can be carried out in stages, according to the 'Milk Ladder'. This is a hierarchy of milk-containing foods, beginning with those least likely to cause a reaction and gradually moving towards being able to drink a glass of milk. In baked form, such as muffins, cakes or malted milk biscuits, cow's milk is less allergenic and may be tolerated sooner than unbaked milk. There is some evidence that including cooked milk in the diet may hasten the resolution of allergy to non-cooked milk[17, 18].
If the child has had IgE type reactions, particularly if they have been severe, then a challenge test should be carried out under close supervision.
Soya formulas have been prescribed in the past for CMPA but soya is also a common allergen, so this is no longer routinely advised. About 10-15% of children allergic to cow's milk will also react to soya. Soya milk also contains isoflavones which have a weak oestrogenic activity.
Other milks, such as pea, oat or coconut, may be used after the age of 2 years, depending on the child's nutritional status and any other allergies they may have. A brand fortified with calcium should be used if available. Rice milk is not recommended for children aged under 4.5 years.
If the symptoms of CMPA persist into older childhood or beyond then patients need to continue to avoid milk and milk products. The proteins in goat's milk and other mammal milks which may be available are almost identical to those found in cow's milk, so those are not suitable substitutes. It is important to maintain an adequate calcium intake. Children who are avoiding cow's milk for allergy reasons should be referred to a paediatric dietician for specialist advice.
Immunotherapy, in which children are given a gradually increasing dose of milk over a period of several months, is one option which has been tried for children with persisting severe allergy. The results have been very promising, although a Cochrane review concluded that further studies of higher quality were necessary before it can be recommended without reservation.
Many people confuse lactose intolerance with CMPA.
Lactose intolerance is an inability to digest lactose, due to an inadequate production of the digestive enzyme lactase. It is generally a condition of older childhood and adulthood. Worldwide it is extremely common, although it is less prevalent in northern European races. It is unusual for babies and young children to be intolerant of lactose, although they do quite commonly develop a transient lactose intolerance following an episode of gastroenteritis.
People with a lactose intolerance can often consume products such as yoghurt and cheese in which the lactose has been altered and they may be able to have small amounts of milk without symptoms. They can generally tolerate lactose-free milk.
Further reading and references
Venter C, Brown T, Meyer R, et al; Better recognition, diagnosis and management of non-IgE-mediated cow's milk allergy in infancy: iMAP-an international interpretation of the MAP (Milk Allergy in Primary Care) guideline. Clin Transl Allergy. 2017 Aug 237:26. doi: 10.1186/s13601-017-0162-y. eCollection 2017.
Cows milk protein allergy in children; NICE CKS, June 2015 (UK access only)
Ludman S, Shah N, Fox AT; Managing cows' milk allergy in children. BMJ. 2013 Sep 16347:f5424. doi: 10.1136/bmj.f5424.
Liao SL, Lai SH, Yeh KW, et al; Exclusive breastfeeding is associated with reduced cow's milk sensitization in early childhood. Pediatr Allergy Immunol. 2014 Aug25(5):456-61. doi: 10.1111/pai.12247.
Hill DJ, Hosking CS; Food allergy and atopic dermatitis in infancy: an epidemiologic study. Pediatr Allergy Immunol. 2004 Oct15(5):421-7.
Osborn DA, Sinn J; Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants. Cochrane Database Syst Rev. 2006 Oct 18(4):CD003664.
Boyle RJ, Ierodiakonou D, Khan T, et al; Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. BMJ. 2016 Mar 8352:i974. doi: 10.1136/bmj.i974.
Vandenplas Y, Koletzko S, Isolauri E, et al; Guidelines for the diagnosis and management of cow's milk protein allergy in infants. Arch Dis Child. 2007 Oct92(10):902-8.
Boyano-Martinez T, Garcia-Ara C, Pedrosa M, et al; Accidental allergic reactions in children allergic to cow's milk proteins. J Allergy Clin Immunol. 2009 Apr123(4):883-8. doi: 10.1016/j.jaci.2008.12.1125. Epub 2009 Feb 20.
Vandenplas Y, De Greef E, Devreker T; Treatment of Cow's Milk Protein Allergy. Pediatr Gastroenterol Hepatol Nutr. 2014 Mar17(1):1-5. doi: 10.5223/pghn.2014.17.1.1. Epub 2014 Mar 31.
Agostoni C, Terracciano L, Varin E, et al; The Nutritional Value of Protein-hydrolyzed Formulae. Crit Rev Food Sci Nutr. 201656(1):65-9. doi: 10.1080/10408398.2012.713047.
Dupont C, Hol J, Nieuwenhuis EE; An extensively hydrolysed casein-based formula for infants with cows' milk protein allergy: tolerance/hypo-allergenicity and growth catch-up. Br J Nutr. 2015 Apr 14113(7):1102-12. doi: 10.1017/S000711451500015X. Epub 2015 Mar 17.
Miraglia Del Giudice M, D'Auria E, Peroni D, et al; Flavor, relative palatability and components of cow's milk hydrolysed formulas and amino acid-based formula. Ital J Pediatr. 2015 Jun 341:42. doi: 10.1186/s13052-015-0141-7.
Host A, Halken S; Cow's milk allergy: where have we come from and where are we going? Endocr Metab Immune Disord Drug Targets. 2014 Mar14(1):2-8.
The Milk Ladder; MAP Guideline
Leonard SA, Nowak-Wegrzyn AH; Baked Milk and Egg Diets for Milk and Egg Allergy Management. Immunol Allergy Clin North Am. 2016 Feb36(1):147-59. doi: 10.1016/j.iac.2015.08.013.
Bloom KA, Huang FR, Bencharitiwong R, et al; Effect of heat treatment on milk and egg proteins allergenicity. Pediatr Allergy Immunol. 2014 Dec25(8):740-6. doi: 10.1111/pai.12283. Epub 2014 Dec 18.
Yeung JP, Kloda LA, McDevitt J, et al; Oral immunotherapy for milk allergy. Cochrane Database Syst Rev. 2012 Nov 1411:CD009542. doi: 10.1002/14651858.CD009542.pub2.
Vandenplas Y; Lactose intolerance. Asia Pac J Clin Nutr. 201524 Suppl 1:S9-13. doi: 10.6133/apjcn.2015.24.s1.02.
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