Cow's milk allergy in children
Exam Tips
- Timing is a key discriminator: IgE reactions are usually immediate (minutes to 2 hours), non-IgE reactions are delayed (2-72 hours).
- Do not diagnose CMA from a positive IgE/SPT result alone; always interpret alongside clinical history and response to elimination-rechallenge.
- In UK exams, first-line feed management is usually extensively hydrolysed formula, not lactose-free formula; consider amino-acid formula if severe or refractory.
- Goat's and sheep's milk are not safe alternatives in most CMA because of cross-reactive proteins.
- Any airway/breathing/circulation compromise after exposure is anaphylaxis until proven otherwise: give IM adrenaline first, then supportive care.
- Persistent eczema, reflux-like symptoms, or constipation that are severe/treatment-resistant should prompt consideration of non-IgE CMA.
Definition
Cow's milk allergy (CMA) in children is a reproducible, immune-mediated reaction to one or more cow's milk proteins (for example casein and whey proteins), usually after ingestion. It is classified as IgE-mediated (typically immediate, within minutes to 2 hours), non-IgE-mediated (usually delayed, 2-72 hours), or mixed disease, and is distinct from non-immune milk intolerance such as lactose intolerance.
Pathophysiology
In IgE-mediated CMA, prior sensitization leads to milk-protein specific IgE binding to mast cells and basophils; re-exposure triggers mediator release (including histamine), causing rapid multisystem symptoms. Non-IgE CMA is largely T-cell driven, producing delayed gastrointestinal and/or skin inflammation; mixed phenotypes show overlap. Clinical expression reflects gut immune immaturity, epithelial barrier dysfunction, and atopic tendency in infancy. See Figure: IgE-mediated immediate hypersensitivity cascade (mast-cell degranulation diagram in standard paediatric allergy/immunology texts).
Risk Factors
- Personal atopy (especially early-onset or severe eczema, asthma, allergic rhinitis)
- Family history of atopy or confirmed food allergy in a first-degree relative
- Existing food allergy or multiple food allergies
- Male sex in childhood
- Poorly controlled asthma (raises risk of severe reactions)
Clinical Features
Symptoms
- Immediate symptoms after milk exposure (minutes to 2 hours): itch, urticaria, lip/tongue swelling, vomiting, wheeze
- Delayed symptoms (2-72 hours): persistent reflux-like symptoms, diarrhoea, constipation with straining, abdominal discomfort, blood or mucus in stool
- Feeding difficulty, food refusal/aversion, unsettled infant/colic-type irritability
- Respiratory symptoms (usually with other features): cough, rhinorrhoea, sneezing, wheeze
- Systemic red flags: lethargy, pallor, collapse, breathing difficulty (possible anaphylaxis/FPIES spectrum)
Signs
- Acute urticaria or angioedema (IgE pattern)
- Eczema flare or persistent eczema not responding to standard treatment
- Perianal erythema, faltering growth, pallor/tired appearance
- Signs of dehydration/shock in severe non-IgE enterocolitis presentations
- Objective wheeze or increased work of breathing in allergic reactions
Investigations
Management
Lifestyle Modifications
- Strict avoidance of cow's milk protein with clear label-reading education and written allergy action plan
- Use suitable milk substitute feed (extensively hydrolysed formula first line in most non-anaphylactic infants; amino-acid formula if severe disease, multiple food allergy, faltering growth, or eHF failure)
- Breastfeeding can continue; if breastfed infant has suspected CMA, maternal cow's milk exclusion with dietetic support and maternal calcium/vitamin D replacement
- Urgent emergency education for families at risk of IgE reactions (recognition of anaphylaxis, when to use auto-injector, call 999)
- Dietitian-led staged reintroduction/tolerance assessment (for example milk ladder in selected non-IgE children when clinically appropriate)
Pharmacological Treatment
Adrenaline (epinephrine) for anaphylaxis
- Adrenaline 1 mg/mL (1:1000) IM: under 6 months 150 micrograms, 6 months-6 years 150 micrograms, 6-12 years 300 micrograms, 12 years and over 500 micrograms; repeat every 5 minutes if needed
Give IM into anterolateral thigh immediately in suspected anaphylaxis; no absolute contraindication in life-threatening anaphylaxis. Children with previous anaphylaxis are typically prescribed adrenaline auto-injectors (for example 150 micrograms or 300 micrograms by weight/age per UK product guidance).
Oral non-sedating H1 antihistamine for mild IgE-mediated reactions
- Cetirizine: 6 months-2 years 2.5 mg twice daily; 2-6 years 2.5 mg twice daily or 5 mg once daily; 6-12 years 5 mg twice daily; 12-17 years 10 mg once daily
Adjunct for cutaneous/mild reactions only; not a substitute for adrenaline in airway, breathing, or circulatory compromise.
Nutritional supplementation when dietary intake is inadequate
- Colecalciferol (vitamin D) age-appropriate prophylactic dosing per UK child guidance
- Elemental calcium supplementation if intake remains insufficient despite formula/diet optimisation
Use after dietetic review; monitor growth and micronutrient status. Avoid unnecessary prolonged exclusion to reduce deficiency risk.
Complications
- Anaphylaxis and rare life-threatening systemic reactions
- Faltering growth and micronutrient deficiencies (especially iron, calcium, iodine, vitamin D, B12) from unsupervised exclusion diets
- Reduced quality of life, anxiety, social restriction, and caregiver burden
- Progression within the atopic march (later asthma, allergic rhinitis, eczema persistence)
- Cross-reactivity with other mammalian milks (for example goat/sheep), risking reactions
- Non-IgE gastrointestinal syndromes: FPIES, food-protein induced allergic proctocolitis, enteropathy; eosinophilic oesophagitis; very rare Heiner syndrome
Prognosis
Overall prognosis is good: most children develop tolerance, particularly in non-IgE CMA which often resolves earlier than IgE-mediated disease. Cohort data show many children become tolerant during early childhood (around half to two-thirds within the first few years, depending on phenotype), while persistence is more likely with high milk-specific IgE/SPT reactivity, severe initial reactions, asthma/allergic rhinitis, and multiple food allergies.
Sources & References
🏥BMJ Best Practice(1)
✅NICE Guidelines(1)
- Cow's milk allergy in children[overview]