Overview
Definition:
Cow's Milk Protein Allergy (CMPA) is an adverse immune response to proteins found in cow's milk
It is broadly classified into IgE-mediated and non-IgE-mediated reactions, which differ significantly in their clinical presentation, diagnostic approach, and management strategies.
Epidemiology:
CMPA is one of the most common food allergies in infants and young children, with estimated prevalence ranging from 2-7.5% in the first year of life, depending on the population studied and diagnostic methods used
IgE-mediated reactions are more common in older children, while non-IgE-mediated reactions are more prevalent in infants.
Clinical Significance:
Accurate differentiation between IgE and non-IgE mediated CMPA is crucial for timely diagnosis and appropriate management
Delayed or incorrect diagnosis can lead to significant nutritional deficiencies, growth faltering, chronic discomfort, and parental anxiety, impacting the child's well-being and development
Understanding these distinctions is vital for pediatric residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Non-IgE mediated: Gastrointestinal symptoms such as vomiting, diarrhea, constipation, abdominal pain, reflux, blood or mucus in stool, and colic
Skin manifestations like eczema
Respiratory symptoms are less common
IgE mediated: Rapid onset of symptoms usually within minutes to two hours of milk ingestion, including urticaria, angioedema, vomiting, diarrhea, wheezing, stridor, and in severe cases, anaphylaxis.
Signs:
Non-IgE mediated: Poor weight gain, failure to thrive, abdominal distension, perianal excoriation due to diarrhea, palpable eczema
IgE mediated: Hives, facial swelling, respiratory distress (wheezing, stridor), hypotension, pallor.
Diagnostic Criteria:
Diagnosis is primarily clinical, supported by an elimination-diet and challenge protocol
Specific diagnostic criteria are less defined for non-IgE mediated CMPA compared to IgE-mediated forms
For IgE-mediated CMPA, positive skin prick tests (SPT) or specific IgE blood tests correlating with clinical symptoms are used, but a gold standard remains oral food challenge.
Diagnostic Approach
History Taking:
Detailed history is paramount
Inquire about onset, timing, and nature of symptoms relative to cow's milk intake, including breast milk if the mother consumes dairy
Ask about family history of atopy, other food allergies, and previous reactions
For IgE-mediated, ask about rapid onset symptoms
For non-IgE mediated, focus on chronic GI issues and poor growth.
Physical Examination:
Assess growth parameters (weight, height, head circumference)
Examine skin for eczema, urticaria, or angioedema
Auscultate lungs for wheezing or stridor
Palpate abdomen for tenderness or distension
Assess hydration status.
Investigations:
Non-IgE mediated: Generally no specific laboratory tests
Stool studies may be done to rule out infection or other causes of diarrhea
Eosinophilic esophagitis or gastroenteritis may be considered if endoscopic biopsies are taken
IgE mediated: Skin prick tests (SPT) with cow's milk proteins and specific serum IgE tests (RAST/ImmunoCAP) can be supportive but require clinical correlation
Negative SPT/IgE does not rule out allergy.
Differential Diagnosis:
For GI symptoms: Infectious gastroenteritis, lactose intolerance, other food intolerances, cow's milk protein-induced enteropathy, eosinophilic gastroenteritis, surgical causes (e.g., intussusception)
For skin symptoms: Atopic dermatitis, viral exanthems, contact dermatitis
For anaphylaxis: Other allergic reactions, sepsis, hypovolemic shock.
Management
Initial Management:
The cornerstone of management for confirmed CMPA is strict avoidance of cow's milk protein
This involves identifying and eliminating all sources of cow's milk protein from the infant's or child's diet.
Medical Management:
Non-IgE mediated: Strict elimination of cow's milk protein from the diet
For breastfed infants, the mother must eliminate dairy from her diet
If formula-fed, use of extensively hydrolyzed casein-whey formula is recommended
For infants with severe reactions or anaphylaxis (IgE-mediated), prompt administration of intramuscular epinephrine is critical
Antihistamines may be used for symptomatic relief of urticaria or itching.
Nutritional Support:
For breastfed infants, maternal elimination diet is preferred
If formula feeding is necessary, extensively hydrolyzed formulas (eHF) are typically the first choice
In cases of severe reactions or multiple food allergies, amino acid-based formulas (AAF) may be required
Ensure adequate calcium and vitamin D intake if dairy is excluded long-term
Monitoring growth and nutritional status is essential.
Oral Food Challenge:
For suspected IgE-mediated CMPA, a medically supervised oral food challenge (OFC) is the gold standard for diagnosis
For non-IgE mediated CMPA, an elimination-challenge protocol is often used to confirm diagnosis, though it may be less standardized
Challenges should be performed in a setting equipped to manage potential allergic reactions.
Prognosis
Factors Affecting Prognosis:
Most children with CMPA, particularly non-IgE mediated forms, outgrow their allergy by 1-3 years of age
Factors influencing prognosis include the severity of the initial reaction, presence of other atopic conditions, and adherence to dietary management
IgE-mediated CMPA may have a longer persistence.
Outcomes:
With strict avoidance, symptoms typically resolve within weeks
Growth parameters improve
Long-term outcomes are generally excellent if managed appropriately
Children may outgrow the allergy and be able to tolerate cow's milk protein later in childhood.
Follow Up:
Regular follow-up with a pediatrician or allergist is recommended to monitor growth, nutritional status, and symptom resolution
Re-evaluation for tolerance, often with a supervised oral food challenge, should be considered around 9-12 months after diagnosis or when appropriate, especially for IgE-mediated CMPA.
Key Points
Exam Focus:
Distinguishing features between IgE and non-IgE mediated CMPA: onset of symptoms (rapid vs delayed), common symptoms (GI vs systemic/anaphylaxis), diagnostic tools (SPT/IgE vs clinical/challenge)
Management principles: strict avoidance and appropriate formula selection (eHF vs AAF)
Role of oral food challenge.
Clinical Pearls:
Always consider CMPA in infants with persistent GI distress, poor growth, or eczema
Differentiate from simple lactose intolerance
Remember that a negative IgE test does not exclude non-IgE mediated allergy
Maternal diet is key for breastfed infants.
Common Mistakes:
Diagnosing CMPA solely on clinical symptoms without exclusion-challenge
Prescribing a hydrolyzed formula without confirming allergy
Not considering anaphylaxis in IgE-mediated reactions
Incorrect interpretation of SPT/IgE results in isolation from clinical history.