Cow’s milk protein allergy (CMPA) is an immune-mediated allergic response to naturally-occurring milk proteins casein and whey. It is common and has spectrum of severity, although can be challenging to diagnosis due to often non-specific presentation in clinical practice.
It is classified according to the aetiology: IgE-mediated, non-IgE-mediated, and mixed.
As one of the most common childhood food allergies in the developed world, it represents a significant burden of morbidity in both primary and secondary care. Prevalence is 7% of formula or mixed-fed infants, and is highest in the first year of life. 0.5% of exclusively breastfed infants suffer from CMPA due to the exposure to cow’s milk protein from the maternal diet via breastmilk, however this is usually a milder presentation.
IgE-mediated: A type-I hypersensitivity reaction. CD4+ TH2 cells stimulate B cells to produce IgE antibodies against cow’s milk protein which trigger the release of of histamine and other cytokines from mast cells and basophils.
Non-IgE-mediated: Involves T cell activation against cow’s milk protein.
- Personal history of atopy (eg. asthma, eczema, allergic rhinitis, other food allergies)
- Family history of atopy (only allergic predisposition is inherited, not specific allergies)
Exclusively breastfeeding is possibly a protective factor
Symptoms can be categorised as follows: speed of onset following exposure, skin, gastrointestinal, respiratory. These also vary according to the aetiology of CMPA.
|IgE-mediated cows’ milk protein allergy||Non-IgE-mediated cows’ milk protein allergy|
|Speed of onset of symptoms|
|Acute and frequently has a rapid onset (up to 2 hours after ingestion)||Non-acute and generally delayed (manifest up to 48 hours or even 1 week after ingestion)|
|Acute urticaria — localized or generalized||Atopic eczema|
|Acute angio-oedema — most commonly of the lips, face, and around the eyes|
|Angioedema of the lips, tongue, and palate||Gastro-oesophageal reflux disease|
|Oral pruritus||Loose or frequent stools|
|Nausea||Blood and/or mucus in stools|
|Colicky abdominal pain||Abdominal pain|
|Diarrhoea||Food refusal or aversion|
|Pallor and tiredness|
|Faltering growth in conjunction with at least one or more gastrointestinal symptoms above (with or without significant atopic eczema)|
|Respiratory symptoms (usually in combination with one or more of the above symptoms and signs)|
|Lower respiratory tract symptoms (cough, chest tightness, wheezing, or shortness of breath)||Lower respiratory tract symptoms (cough, chest tightness, wheezing, or shortness of breath)|
|Upper respiratory tract symptoms (nasal itching, sneezing, rhinorrhoea, or congestion [with or without conjunctivitis])|
It is also important to consider CMPA in patients with atopic eczema, gastro-oesophageal reflux disease or chronic gastrointestinal symptoms who are not responding adequately to treatment. Diagnosis may be one of exclusion in these patients and confirmed by successful treatment for CMPA.
If suspected, take a careful allergy-focussed history:
- Personal and family history of atopy
- Diet and feeding history of infant
- Mother’s diet if breastfed
- Any previous management used for symptoms
- Which milk/foods
- Age of onset
- Speed of onset following exposure
- Severity and frequency of occurrence
- Setting of reaction
- Reproducibility of symptoms
General physical examination of patient with a focused gastrointestinal examination, specifically signs of malnutrition.
Review growth charts
Signs of atopic comorbidities such as asthma, eczema, allergic rhinitis.
- Food intolerance (eg. lactose) may present as abdominal pain and diarrhoea following exposure to certain foodstuffs
- Allergic reaction to other food or non-food allergens
- Anatomical abnormalities such as Meckel’s diverticulum
- Chronic gastrointestinal disease (e.g. gastro-oesophageal reflux disease, coeliac disease, inflammatory bowel disease, constipation, gastroenteritis)
- Pancreatic insufficiency (eg. as a complication of cystic fibrosis)
- Urinary tract infections
It is usually sufficient to clinically diagnose CMPA based on history and examination, however if this is unclear then a blood test looking for specific IgE antibodies (previously known as a RAST-radioallergosorbent- test) to cows milk protein can be useful if IgE-mediated CMPA is suspected. Although this is a sensitive test it has low specificity, resulting in false positives, meaning patients can be sensitised to cow’s milk protein (i.e. have allergen-specific IgE) but not be allergic.
Refer for RAST test if there is:
- Faltering growth with at least of the above symptoms
- One or more acute systemic or severe delayed reactions
- Confirmed IgE-mediated food allergy with asthma
- Persistent parental suspicion of a food allergy despite lack of clear history
- Clinical suspicion of multiple food allergies, especially with concomitant significant eczema
Non-IgE-mediated CMPA is clinically diagnosed.
Other blood tests such as a full blood count with haematinics may be useful if iron-deficiency anaemia is suspected although are not routinely required for diagnosis of CMPA.
CMPA is managed by avoidance of cow’s milk in all forms, including in mother’s diet if she is breastfeeding.
An elimination diet is required for a least 6 months or until infant is 9-12 months old, with re-evaluation of the infant every 6 to 12 months to assess for tolerance to cow’s milk protein. The MAP guideline milk ladder can be helpful for patients.
Nutritional counselling and regular monitoring of growth
In infants who are formula-fed, their milk is replaced with a hypoallergenic formula which come in two forms:
- Extensively hydrolysed formula: cheaper, first-line formula made from cow’s milk but the casein and whey are broken down into smaller peptides which are less immunogenic. 90% of children with CMPA will respond to this.
- Amino acid formula: more expensive, second-line formula for the 10% children who continue to have symptoms despite using hydrolysed formula or who have very severe symptoms.
Soya-based formulas are not recommended in infants <6 months old due to the weak oestrogenic effect of isoflavones, and absorption of minerals and trace elements may be inhibited by phytate found in this milk.
Serious complications relate to malabsorption or reduced intake due to symptoms presenting as chronic iron-deficiency anaemia and faltering growth, although this is effectively treated by allergen avoidance. Anaphylaxis is rare and most patients will be milk tolerant by early childhood.