Threshold heterogeneity and dose‐related clinical reaction profiles in infantile food protein‐induced enterocolitis syndrome

Background

Oral food challenge (OFC) protocols in food protein‐induced enterocolitis syndrome (FPIES) often select starting doses with consideration of prior reaction severity, implying that dose may influence reaction intensity; however, patient‐level evidence linking antigen dose to reaction profiles remains limited.

Objective

To characterize threshold heterogeneity and compare clinical reaction profiles between diagnostic and reactive threshold OFCs within individual patients.

Methods

In this prospective study, 54 infants with OFC‐confirmed FPIES (egg yolk, 36; cow's milk, 18) underwent threshold characterization at 0.001 g/kg (ultra‐low) and 0.01 g/kg (low); all had previously reacted at a diagnostic OFC (median 0.38 g/kg). For the 30 reacting at a threshold challenge, the primary endpoint was objective reaction intensity (vomiting, examination signs); treatment intensity and a composite burden category were supporting measures.

Results

Of 54 patients, 12 (22%) reacted at 0.001 g/kg, 18 (33%) at 0.01 g/kg, and 24 (44%) tolerated both. Among the 30 threshold reactors, reactions were objectively milder than at the diagnostic OFC: median vomiting 2 (IQR 2–3) versus 4 (4–6) ( p  < .001), pallor 27% versus 63% ( p  = .019), decreased activity 43% versus 80% ( p  = .007). No ICG‐defined severe features (hypotension/shock, severe lethargy) occurred at either OFC. Treatment intensity was also lower (intravenous fluid and prolonged observation each 27% versus 67%; both p  < .001).

Conclusion

Reactions at ultra‐low and low threshold doses were objectively milder than at diagnostic doses within patients, while clinically meaningful reactions still occurred. These findings support systematic threshold assessment beginning at 0.001 g/kg, independent of diagnostic OFC clinical burden.

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