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Cow’s Milk Allergy

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Overview

Cow’s milk allergy (CMA) is a reproducible immune-mediated allergic response to one or more proteins in cow’s milk. It can be classified according to the immunologic mechanism and timing of symptoms:

  • Immunoglobulin E (IgE)-mediated food allergy:
    • Due to specific IgE antibodies to cow’s milk proteins
    • Produces immediate and consistently reproducible symptoms
    • Reactions usually occur within 20-30 minutes to 2 hours of ingestion
  • Non-IgE-mediated food allergy:
    • Due to cell-mediated hypersensitivity which is delayed compared to IgE
    • Usually presents within 2-72 hours of ingestion 
  • Mixed IgE and non-IgE allergy

Definitions

Food sensitisation describes the production of serum-specific IgE to food allergens without the features of an allergic reaction.

Food intolerances are non-immune adverse reactions to foods that are distinct from food allergies. They present with non-specific gastrointestinal symptoms: 

  • For example, in lactose intolerance, there is no immune element to the signs and symptoms experienced. Lactose cannot be digested, so it remains in the gastrointestinal tract, resulting in water entering the colon down a water potential gradient. This leads to diarrhoea.

Epidemiology

  • CMA is one of the most common food allergies after egg allergy
  • Mild-moderate non-IgE-mediated allergy is the most common presentation
  • Almost all cases present in < 1-year-olds
  • CMA is twice as common in boys

Risk Factors

  • Known allergy
  • Atopy (e.g. asthma, eczema)
  • Family history of allergy
  • Family history of atopy

Presentation

In general, IgE-mediated and non-IgE-mediated CMA can be differentiated based on clinical features and timeframes:

  • Timeframe:
    • IgE-mediated – within minutes to up to 2 hours after ingestion
    • Non-IgE-mediated – usually 2-72 hours after ingestion
  • Gastrointestinal:
    • IgE-mediated: angioedema of the lips/tongue/palate, oral pruritus, nausea, colicky abdominal pain, vomiting, diarrhoea 
    • Non-IgE-mediated: gastro-oesophageal reflux disease, vomiting, diarrhoea, blood/mucus in stools, abdominal pain, colicky abdominal pain, food refusal, constipation, perianal redness, pallor/tiredness, faltering growth – suggests severe allergy
  • Skin:
    • IgE-mediated: pruritus, erythema, urticaria, angioedema, flare of pre-existing eczema
    • Non-IgE-mediated: pruritus, erythema, eczema
  • Respiratory:
    • IgE-mediated: lower respiratory tract features (wheezing, shortness of breath, cough and upper respiratory tract features (nasal itching, sneezing, rhinorrhoea, congestion, conjunctivitis) 
    • Non-IgE-mediated: lower respiratory tract features only
  • Other:
    • IgE-mediated: anaphylaxis
    • Non-IgE-mediated: n/a

Diagnosis

Overview

Diagnosis is clinical, however, allergy testing may be considered for IgE-mediated CMA in a specialist setting which may include:

  • Skin prick testing
  • Serum-specific IgE testing

There are no reliable tests to confirm the diagnosis of non-IgE-mediated allergy.

Management

Overview

  • If there is failure to thrive or severe symptoms: refer to paediatrician
  • If formula-fed:
    • Extensively hydrolysed formula milk is first-line
    • Amino acid-based formula milk may be used if there is no response or if CMA is severe
  • If breastfed:
    • Continue breastfeeding but eliminate cow’s milk protein from maternal diet
      • Calcium supplements should be considered to prevent deficiency
    • Use extensively hydrolysed formula milk when breastfeeding stops until 12 months of age and at least for 6 months

Complications

  • Stress/anxiety for carers
  • Reduced quality of life
  • Malnutrition
  • Development of other atopic conditions (e.g. asthma, eczema, allergic rhinitis)
  • Cross-reactivity with other animal’s milk
  • Anaphylaxis
  • Enterocolitis, particularly in non-IgE-mediated allergy
  • Eosinophilic oesophagitis – vomiting, food aversion, and faltering growth
  • Heiner’s syndrome – milk-induced pulmonary disease characterised by haemoptysis and anaemia

Prognosis

  • Around half of the children with IgE-mediated CMA will become milk tolerant by 5 years
  • Non-IgE-mediated CMA is generally associated with a faster rate of resolution and most children will become milk tolerant by 3 years

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