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Cow’s milk protein allergy


A six-week-old baby is referred to you for urgent assessment for blood-stained loose stools. He was born at term and there were no antenatal/postnatal complications of note. He received IM Vitamin K at birth. He was initially breastfed for two weeks and then started on feeds with cow’s milk formula. He is thriving well and the clinical examination was unremarkable.


Bottom line

  • Cow’s milk protein allergy is an immunological reaction to one or more cow’s milk proteins.
  • Cow’s milk protein allergy can be IgE/non-IgE-mediated.
  • It can present with symptoms from the gastrointestinal, respiratory system, the skin or as an acute anaphylactic reaction
  • It is diagnosed with a focused clinical history and certain tests (skin prick testing, RAST ) can be used to aid diagnosis
  • Allergen avoidance and the use of eHF/AAF are the main management approaches


What is cow’s milk protein allergy (CMPA)?

Cow’s milk protein allergy refers to an immunological reaction to one or more milk proteins. The prevalence of CMPA varies from 2% to 7.5%. It can develop in exclusively or partially breastfed infants or when CMP is introduced into the feeding regime. The incidence of CMPA is lower in exclusively breastfed babies compared to babies who are on formula feeds.


What’s the pathophysiology?

CMPA results from an immunological reaction to milk proteins. The immunological basis distinguishes CMPA from other adverse reactions to milk proteins e.g. lactose intolerance.

CMPA can be IgE-mediated, non-IgE-mediated and mixed reactions. Many non-IgE-mediated reactions are believed to be T-cell-mediated. IgE- mediated reactions are acute, often have a rapid onset and can be a manifestation of the atopic diathesis. Non-IgE-mediated reactions are generally characterized by delayed and non-acute onset. Finally, mixed reactions involve a mixture of both IgE and non-IgE-mediated reactions.


What are the signs and symptoms?

CMPA can manifest with one or more of the following symptoms:

  • Skin: pruritus, erythema, acute urticaria, acute angioedema, atopic eczema
  • Gastrointestinal system: nausea, vomiting, diarrhoea, colicky abdominal pain, reflux, blood/mucous in stools, food refusal/aversion,  perianal redness, faltering growth
  • Respiratory system: nasal itching, sneezing, rhinorrhoea +/- conjunctivitis, cough, wheezing, shortness of breath, chest tightness
  • Signs and symptoms of an acute anaphylactic reaction


How is it diagnosed?

CMPA is diagnosed clinically with a focused history and the presence of the signs and symptoms described above.

Elements of a focused allergy history should be:

  • Personal history of atopic eczema or previous allergic reactions
  • Family history of  atopy or previous allergic reactions to food
  • Detailed feeding history
  • Details of previous treatment and the results of it
  • Any response to elimination and reintroduction of food
  • Presenting symptom: age of onset, speed of onset, suspected allergen, the setting of the reaction (e.g. school), duration, frequency, severity

The following diagnostic options could be considered:

  • Skin prick testing, blood tests for specific IgE antibodies (RAST) to suspected types of food or co-allergen (when IgE-mediated CMPA is suspected). High IgE concentrations and a larger wheal on skin prick test give a higher probability of clinical allergy. However, an observational study showed that 5.6% of the infants had a positive skin prick test response but only 2.7% showed clinical signs of cow’s milk allergy. The results from this study show that the skin prick test response should not be used in isolation but in conjunction with a relevant clinical history for the diagnosis of CMPA.
  • Elimination diet trial. Improvement of symptoms on cow’s milk exclusion diet (or removal of cow’s milk protein from the mother’s diet for breastfed babies) and recurrence of symptoms on reintroduction is highly suggestive of non-IgE mediated cow’s milk protein allergy.


What’s the differential diagnosis?

The differentials of cow’s milk protein allergy include:

  • Non-immunological reactions to food such as lactose intolerance
  • Allergic reactions to other food allergens such as soy, wheat
  • Infections: gastrointestinal infections, urinary tract infections
  • Coeliac disease for babies above six months
  • Cystic fibrosis or non-CF–related pancreatic insufficiency



For IgE mediated reactions exclusion of cow’s milk from the diet is recommended. For non-IgE reactions both cow’s milk and soy should be removed from the diet because of the risk of cross-reactivity.

For formula-fed babies, a hydrolyzed formula can be used. If symptoms do not improve within two to eight weeks, an amino acid formula should be commenced. Hydrolyzed formulae are extensively broken down into smaller peptides that are not easily recognized by the immune system. Amino acid based formulas contain no peptides to be recognized by IgE, hence why they are recommended when a poor response to hydrolyzed formulas is achieved. Amino acid based formulas are the first choice for formula-fed babies with a history of previous anaphylaxis or severe skin/gut reactions to cow’s milk. The role of the dietitian is important to ensure appropriate nutrition when the above steps have to be taken.

Breastfed infants with CMPA should be treated with allergen avoidance. This is achieved with a maternal exclusion diet avoiding food containing cow’s milk protein. The elimination diet should continue for at least two weeks and up to four weeks in cases of allergic colitis or atopic dermatitis. During the elimination trial, the mother should receive calcium/Vitamin D supplements. In most cases, symptoms will improve within two to four weeks following the commencement of the elimination diet. Once shown to help, cow’s milk should then be reintroduced to prove that it is the causal agent. Once the diagnosis is confirmed, the infant should remain on the elimination diet for at least five months or until one year of age, when cow’s milk can be reintroduced, usually at home.

For IgE-mediated reactions, an emergency management plan should be provided for the family’s reference or for nursery/school. For the management of those reactions, antihistamines and adrenaline autoinjectors could be used. Autoinjectors are indicated for patients who meet the criteria of the European Academy of Allergy and Clinical Immunology’s Management of Anaphylaxis guideline.


Selected references

Yvan Vandenplas et al. Guidelines for the diagnosis and management of cow’s milk protein allergy in infants. Archives of Disease in Childhood 2007;92:902-908.

Food allergy in children and young people, National Institute for Health and Clinical Excellence, February 2011.

Ludman et al. Management of cow’s milk allergy in children. BMJ 2013;347:f5424

EAACI Anaphylaxis guideline, version 4.5, June 2013


  • Dr Thanos Konstantinidis is a paediatric trainee in the North Western Deanery, England. Special interests include GlobalHealth, Medical Leadership, Paediatric Infectious diseases/immunology #NWSOP



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