Cow’s milk protein allergy
A six-week-old baby is referred to you for urgent assessment of blood-stained loose stools. He was born at term, with no antenatal/postnatal complications.
He received IM Vitamin K at birth. He was initially breastfed for 2 weeks, then started on 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- or non-IgE-mediated.
It can present with symptoms from the gastrointestinal or respiratory systems, the skin, or as an acute anaphylactic reaction.
It is diagnosed based on 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 regimen. The incidence of CMPA is lower in exclusively breastfed babies than in babies on formula feeds.
What’s the pathophysiology of CMPA?
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, or mixed.
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 characterised by delayed and non-acute onset. Finally, mixed reactions involve both IgE- and non-IgE-mediated responses.
What are the signs and symptoms of CMPA?
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 CMPA 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 the 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
Consider these tests:
- Skin prick testing and blood tests for specific IgE antibodies (RAST) to suspected food types or co-allergens (when IgE-mediated CMPA is suspected). High IgE concentrations and a larger wheal on the skin prick test give a higher probability of clinical allergy. However, an observational study found that 5.6% of 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 a 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 are 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
Management
Exclusion of cow’s milk from the diet is recommended for IgE-mediated reactions. Because of the risk of cross-reactivity, both cow’s milk and soy should be removed from the diet in cases of non-IgE-mediated reactions.
A hydrolysed formula can be used for formula-fed babies. If symptoms do not improve within two to eight weeks, an amino acid formula should be commenced. Hydrolysed formulae are extensively broken down into smaller peptides that are not easily recognised by the immune system.
Amino acid-based formulas contain no peptides to be recognised by IgE, which is why they are recommended when a poor response to hydrolysed formulas is achieved. They are the first choice for formula-fed babies with a history of previous anaphylaxis or severe skin/gut reactions to cow’s milk.
Breastfed infants with CMPA should be treated with allergen avoidance. This is achieved with a maternal exclusion diet that avoids foods 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 2 to 4 weeks of commencing the elimination diet.
Once shown to be helpful, cow’s milk should be reintroduced to confirm 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.
An emergency management plan should be provided for the family’s reference or for the nursery/school. Antihistamines and adrenaline autoinjectors could be used to manage IgE-mediated reactions. 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
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
