A randomized trial of oral immunotherapy for pediatric cow's milk‐induced anaphylaxis: Heated vs unheated milk

BACKGROUND: Severe reactions may develop during cow's milk (CM) oral immunotherapy (OIT). We investigated the safety and efficacy of low‐dose OIT with heated milk (HM) or unheated milk (UM) in children with anaphylaxis. METHODS: Children with symptom onset after ingestion of 3‐mL HM on a double‐blind, placebo‐controlled food challenge were randomly assigned to the HM (n = 17) or UM (n = 16) group. HM group ingested milk powder heated at 125°C for 30 seconds, whereas the UM group used UM. Patients were hospitalized for 5 days; the HM or UM was gradually increased to 3 mL/day; 3‐mL/day ingestion was continued at home. One year later, the patients underwent 2‐day consecutive 3‐ and 25‐mL HM‐oral food challenges (OFCs) after 2‐week avoidance. RESULTS: At baseline, milk‐ and casein‐specific immunoglobulin E (IgE) levels were 56.0 and 51.4 kUA/L in the HM group, and 55.2 and 65.6 kUA/L in the UM group, respectively. One year later, 35% and 18% in the HM group and 50% and 31% in UM group passed the 3 and 25 mL OFCs, respectively. Rates of moderate or severe symptoms and respiratory symptoms per home dose were significantly lower in the HM than in the UM group (0.7% and 1.2% vs 1.4% and 2.6%, respectively, P < .001). β‐lactoglobulin‐specific IgG(4) levels significantly increased from baseline only in the UM group, whereas casein‐specific IgG(4) levels significantly increased from baseline in both groups. CONCLUSIONS: HM‐OIT induced immunological changes more safely than the UM‐OIT. The possibility of lower treatment efficacy with HM‐OIT needs to be evaluated in larger studies.