Cow Milk Protein Allergy (CMPA)
Cause and Pathophysiology
Cow milk protein allergy (CMPA) is an immune reaction to proteins within cow’s milk
Classification by underlying immune mechanism: [BSACI]
- IgE-mediated CMPA: typically causes immediate symptoms (usually within minutes to 2 hours of exposure)
- Non-IgE-mediated CMPA: typically causes delayed symptoms (often occurring hours to days after exposure)
Do NOT confuse CMPA with lactose intolerance, which is a distinct condition. They are often confused with one another due to the overlapping GI symptoms. [BSACI]
| Feature | CMPA (cow milk protein allergy) | Lactose intolerance |
|---|---|---|
| Mechanism | Immune-mediated reaction to cow’s milk protein | Non-immune-mediated reaction; occurs due to lactase deficiency |
| Trigger | Milk protein | Milk sugar (lactose) |
| Presentation | Onset typically in infancy
Multisystem symptoms (e.g. GI, skin, respiratory, cardiovascular) |
Subtle progressive onset, typically diagnosed in later childhood, adolescence or adulthood
Strictly GI symptoms only (e.g. abdominal discomfort, bloating, flatulence, diarrhoea) |
| Natural history | Typically resolves with age, most children outgrow CMPA by adulthood | Tends to persist, but the degree of tolerance may vary over time |
Risk Factors and Associations
CMPA is associated with other atopic conditions: [BSACI]
- Personal or family history of atopy
- Other food allergies
- Asthma
- Allergic rhinitis
Clinical Features
Shared features: [BSACI]
| Age of onset | Typically during infancy, at 3-6 m/o
Onset after 12 m/o is uncommon |
| Natural history | CMPA has a favourable outcome
Only 1 in 20 remain allergic in adulthood |
Otherwise, clinical features depend on the type of CMPA: [BSACI]
| Type | Onset after exposure | Clinical features |
|---|---|---|
| IgE-mediated CMPA | Immediate, typically within minutes (or up to an hour) after exposure | Multisystem allergic reaction
Anaphylaxis is possible |
| Non-IgE-mediated CMPA | Delayed, typically hours (or sometimes days) after exposure | Mainly GI and/or cutaneous features:
Anaphylaxis is not a feature, and respiratory features are not typically dominant Other phenotypes:
|
Investigation and Diagnosis
The work-up and diagnosis largely depend on the suspected CMPA type (based on clinical suspicion – see above)
Suspected IgE-mediated CMPA
1st line: skin prick test and/or serology (cow’s milk-specific IgE) [BSACI]
- +ve skin prick test: wheal ≥3 mm above the negative control
- +ve serology: ↑ cow’s milk-specific IgE
A +ve skin prick test and/or cow’s milk-specific IgE + compatible clinical features can diagnose IgE-mediated CMPA
If diagnosis remains uncertain after 1st line tests → oral food challenge [BSACI]
- Involves giving the patient cow’s milk in a supervised setting
- +ve test: symptoms are reproduced
Suspected non-IgE-mediated CMPA
Diagnosis is based on a trial of cow’s milk elimination followed by reintroduction [BSACI]
- Improvement during elimination and recurrence of symptoms on reintroduction supports the diagnosis
There are NO validated allergy tests that can confirm non-IgE-mediated CMPA. [BSACI]
Management
Cornerstone of management: avoidance of cow’s milk + replacement feeding [BSACI]
- 1st line: extensively hydrolysed formula (eHF)
- 2nd line (if inadequate response to eHF, or there has been anaphylaxis or faltering growth): amino acid formula (AAF)
Goat’s and sheep’s milk are not suitable alternatives to cow milk because of cross-reactivity [BSACI]
Other management: [BSACI]
- Dietitian assessment (esp. to ensure adequate calcium and overall nutritional intake)
- In IgE-mediated CMPA
- Provide advice on recognising and managing acute allergic reactions
- Patients at risk of severe reactions may require an emergency management plan and adrenaline auto-injector
ALL patients should be reassessed for tolerance (as CMPA often resolves with age): [BSACI]
- Start reassessing from 12 months of age, every 6-12 months
- Graded reintroduction with a milk ladder is recommended when there are improvements in tolerance
- Whether this is done at home or under hospital supervision depends on severity and risk
~2/3 of children’s CMPA resolves by school age [BSACI]