Cow Milk Protein Allergy

Cow milk protein allergy is an adverse immunological reaction to cow's milk proteins (casein, beta lactoglobulin, alpha lactalbumin), the commonest food allergy in infancy.

• Prevalence about 2 to 3 percent of infants (by challenge proven diagnosis), though perceived rates are much higher; onset often within the first weeks of exposure (first formula, first weaning).
• Types:
  • IgE-mediated (immediate, within minutes to 2 hours): urticaria, angioedema, vomiting, wheeze, rhinitis, conjunctivitis, abdominal pain, anaphylaxis (about 40 to 50 percent of CMPA in some series).
  • Non-IgE-mediated (delayed, hours to days): reflux, vomiting, colic, diarrhoea, constipation, blood and mucus in stool, atopic eczema, poor growth, food refusal; includes food protein induced allergic proctocolitis, enteropathy, enterocolitis (FPIES: repetitive vomiting 1 to 4 hours after ingestion, lethargy, pallor, and hypotension), eosinophilic gastrointestinal disease.
  • Mixed.
• Risk factors: family history of atopy, eczema, other food allergy, caesarean delivery, early formula exposure after breastfeeding, genetic factors.
• Natural history: about 50 percent tolerate by 1 year, 75 percent by 3 years, and 80 to 90 percent by 5 years (IgE-mediated and higher IgE persist longer).
• Complications: faltering growth, iron deficiency anaemia, nutritional deficiencies (calcium, vitamin D), anaphylaxis, reduced quality of life, risk of other atopic disease.

• Skin: eczema (moderate to severe, unresponsive to treatment), urticaria, angioedema, perioral rash.
• Gastrointestinal: regurgitation, vomiting, colic like distress, diarrhoea, constipation (often soft stools with straining), blood or mucus in stool, food refusal or aversion, perianal redness, faltering growth.
• Respiratory: runny nose, wheeze, cough (rarely isolated).
• Anaphylaxis: facial swelling, stridor, wheeze, pallor, floppiness, hypotension, collapse.
• FPIES: delayed profuse vomiting, lethargy, pallor, diarrhoea; may progress to shock.
• Examination: growth, eczema extent, signs of anaemia or dehydration, abdominal, perianal.
• Red flags: anaphylaxis or airway involvement, faltering growth, severe eczema, FPIES with dehydration or shock, iron deficiency anaemia, protein losing enteropathy, bloody diarrhoea with systemic illness (infection, necrotising enterocolitis).

• Allergy focused history is key (timing, symptoms, reproducibility, atopy).
• IgE-mediated: skin prick test (wheal of 3 mm or more above negative control) or serum specific IgE to cow's milk (0.35 kUA/L or more indicates sensitisation; levels above about 5 kUA/L in infants are highly predictive of reaction), performed by an allergy service; oral food challenge under supervision (the most reliable test) when uncertain.
• Non-IgE-mediated: no reliable test; diagnostic elimination of cow's milk protein for 2 to 4 weeks, followed by supervised reintroduction (milk challenge) to confirm; a positive challenge shows return of symptoms within hours to 2 days.
• Atopy patch tests and food specific IgG are not useful.
• Investigations for complications: full blood count, ferritin, albumin, growth assessment, endoscopy and biopsy for eosinophilic disease.

• Dietary elimination of cow's milk protein with dietitian input; always check labels; avoid cross contact; remember hidden sources (butter, cheese, whey, casein, lactoglobulin, cakes, sauces).
• Breastfed infants: continue breastfeeding; the mother excludes cow's milk and dairy products from her diet while breastfeeding (for 2 to 4 weeks then review); mother takes calcium 1000 mg daily and vitamin D 10 micrograms (400 IU) daily.
• Formula fed infants:
  • Mild to moderate symptoms: extensively hydrolysed formula (eHF) for 6 to 12 months or until about 9 to 12 months of age, whichever is longer.
  • Severe symptoms, anaphylaxis, faltering growth, FPIES, eosinophilic oesophagitis, multiple food allergies, or failure of eHF within 2 to 4 weeks: amino acid formula (AAF).
  • Soya formula only after 6 months in selected cases (cross reactivity in 10 to 15 percent of non-IgE and soy allergy); avoid rice milk as a main drink for children under 4.5 years because of arsenic content; plant based milks (oat, almond, coconut) are not nutritionally adequate as the main milk below 2 years unless fortified and under dietitian supervision; goat's and sheep's milk are cross reactive and unsuitable.
• Weaning: introduce solids at around 6 months (not before 4 months) without cow's milk; include other allergens (egg, peanut) early as appropriate; avoid delay.
• Supplements: calcium (age 1 to 3 years about 350 to 700 mg daily; ensure total intake 700 mg for 1 to 3 years, 1000 mg for 4 to 8 years, 1300 mg for 9 to 18 years) and vitamin D 400 IU daily as needed.
• Emergency plan for IgE-mediated CMPA:
  • Antihistamine for mild reactions: cetirizine 2.5 mg orally twice daily (age 6 to 11 months: 2.5 mg once daily; 1 to 5 years: 2.5 mg twice daily; 6 years and above: 5 to 10 mg once daily).
  • Anaphylaxis: adrenaline (epinephrine) 0.01 mg/kg intramuscularly (0.01 mL/kg of 1 mg/mL), in practice 150 micrograms for under 6 years (auto injector 150 micrograms for 7.5 to 25 kg), 300 micrograms for 6 to 12 years, 500 micrograms (or 300 micrograms) for over 12 years, repeated after 5 minutes if no improvement; call emergency services; lie flat with legs raised.
  • Prescribe two adrenaline auto injectors, train carers, provide a written action plan.
• Reintroduction (milk ladder): after 6 to 12 months of elimination for non-IgE disease, a graded reintroduction at home starting with baked milk (e.g., biscuit) progressing to yoghurt, cheese, and fresh milk over weeks, if symptoms were mild; supervised in hospital for severe, IgE-mediated or FPIES history. Retest IgE-mediated allergy every 6 to 12 months.
• Follow up with a dietitian and allergist; monitor growth, ferritin; refer for suspected IgE-mediated disease, severe symptoms, faltering growth, multiple food allergies, or failure to improve.