Cow milk protein allergy mimics in infancy

Table 4 How clinical history can help differentiate cow milk protein allergy from other mimicking conditions

Condition	Key features in clinical history	How clinical history helps differentiate from CMPA
CMPA (IgE-mediated and non-IgE-mediated)	Symptoms often begin in the first few months after cow's milk introduction; Can present with gastrointestinal (vomiting, diarrhea), dermatological (eczema, urticaria), respiratory (wheezing, coughing), and systemic (anaphylaxis) symptoms	Symptoms directly linked to cow's milk exposure; May involve multiple systems (gastrointestinal, skin, respiratory) simultaneously; Family history of atopic diseases increases the likelihood of CMPA
GERD	Common in infants, often linked with post-feeding regurgitation, vomiting, irritability, & back arching; Often exacerbated by overfeeding, positional changes, or lying down	GERD symptoms are primarily gastrointestinal (vomiting, regurgitation) and often responsive to anti-reflux treatments (H2 blockers or proton pump inhibitors); No skin, respiratory, or systemic involvement
Lactose intolerance	Usually present after the introduction of dairy (often after weaning) or with high-lactose-containing formula or milk; Symptoms mainly gastrointestinal (bloating, diarrhea, abdominal cramping)	Symptoms occur specifically after lactose ingestion and are not associated with other systemic reactions (e.g., skin rashes or respiratory symptoms); Rare in infants but can occur in older children
FPIES	Presents with delayed gastrointestinal symptoms (vomiting, diarrhea, lethargy) after ingestion of a trigger protein (cow's milk, soy); Episodes often occur hours after ingestion	Symptoms typically emerge hours after milk ingestion (delayed reaction); No allergic (IgE-mediated) symptoms like urticaria or anaphylaxis; Symptoms resolve with dietary elimination of the trigger
EoE	Chronic symptoms of reflux, vomiting, dysphagia, or food impaction; History of food allergies or atopic diseases is common; Symptoms may persist despite reflux treatments	EoE often presents with chronic vomiting or feeding difficulties, but without systemic allergic manifestations; No immediate or IgE-mediated reactions; Requires biopsy for diagnosis
Casomorphin-induced gastrointestinal disorders	May include symptoms like bloating, diarrhea, and abdominal pain after milk consumption; History may show improvement with dairy-free diet	Symptoms are generally isolated to gastrointestinal issues, unlike CMPA, which involves a broader spectrum (e.g., skin, respiratory); No immediate allergic response or anaphylaxis

The table shows that each condition has distinct features in terms of symptom timing, response to dietary changes, and involvement of multiple organ systems, all of which can guide the clinician toward the correct diagnosis. H2 blockers: Histamine-2 receptor antagonists. CMPA: Cow milk protein allergy; EoE: Eosinophilic esophagitis; FPIES: Food protein-induced enterocolitis syndrome; GERD: Gastroesophageal reflux disease.