Biomarkers of Tolerance to Baked Milk in Cow's Milk-Allergic Children at High Risk of Anaphylaxis

Consuming baked milk (BM) may accelerate tolerance in cow's milk-allergic (CMA) children. In high-risk patients, controlled BM-based oral food challenge (BM-OFC) is recommended, as the benefits can outweigh the risks of a prolonged exclusion diet. Objectives: To identify predictive biomarkers for BM-OFC outcomes in a cohort at high risk of anaphylaxis and compare the OFC thresholds for baked and pasteurized cow´s milk protein (CMP).

We performed a prospective study of children (≥12 months to <6 years) with a history of CMA. Testing at diagnosis involved prick testing, specific IgE (sIgE) for CM and components, sIgG4, and the basophil activation test (BAT). Patients underwent a BM-OFC aiming for a cumulative dose of 1 g of CM protein. BM-tolerant children subsequently underwent a CM-OFC to confirm CMA.

The study population comprised 50 patients (66% with a history of anaphylaxis). A reaction was recorded during BM-OFC in 36% of patients (39% with anaphylaxis). The median reactivity threshold was 138 mg of CMP. Risk factors for BM allergy included history of anaphylaxis, age >3 years, elevated CM-sIgE and casein-sIgE, and a positive BAT result. The cut-offs were as follows: >5 mm for skin prick testing with casein, ≥8.5 kUA/L for CM-sIgE, and ≥5.7 kUA/L for casein-sIgE. These made it possible to distinguish BM-allergic patients from CMA patients who tolerated BM. Among BM-tolerant patients, the CM-OFC threshold was 270 mg, with 43.8% reacting to <100 mg (40% with anaphylaxis).

BM-OFC is not risk-free. Nevertheless, two-thirds of high-risk CMA children were BM-tolerant and benefited from early introduction of BM products. Patient selection can be guided by biomarkers and a prior history of anaphylaxis to baked goods. The reactivity threshold to pasteurized milk was less than half of the tolerated dose of BM (1000 mg).