# Prolonged Multi-food Food Protein-Induced Enterocolitis Syndrome (FPIES) With Yolk Specificity and Reproducible Cytokine Responses During Serial Oral Food Challenges

## TL;DR

A child with a rare food allergy showed prolonged reactions to cow's milk and egg yolk, with specific immune responses and possible links to early-life viral infection.

## Contribution

This case report identifies prolonged multi-food FPIES with yolk specificity and reproducible cytokine patterns linked to early-life CMV infection.

## Key findings

- Serial oral food challenges showed consistent increases in TNF-α, IL-8, and TARC/CCL17 after symptom onset.
- Low serum and salivary TGF-β levels were observed, indicating deficient regulatory signaling.
- Early-life CMV infection may have modulated the disease trajectory through mucosal inflammation.

## Abstract

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy of infancy, with cow’s milk as a classic trigger and egg yolk increasingly recognized in Japan. We report a term female who developed chronic FPIES to cow’s milk in early infancy, followed by acute FPIES to heated egg yolk at six months. Perinatal cytomegalovirus (CMV) infection was documented by positive CMV IgM and persistent urine CMV polymerase chain reaction (PCR) positivity. Symptoms improved with an extensively hydrolyzed formula, yet serial hospital-based oral food challenges (OFCs) over five years repeatedly reproduced emesis two to four hours after milk or heated yolk ingestion, while tolerance to whole egg white (40 g) was achieved by 3.5 years. Across multiple OFCs, we observed consistent increases in TNF-α, IL-8, and TARC/CCL17 approximately 24 hours after symptom onset, alongside persistently low serum and salivary TGF-β. These immune patterns suggest a reproducible pro-inflammatory phenotype with deficient regulatory signaling. Given the biological plausibility that early-life CMV may transiently disrupt epithelial integrity and amplify mucosal cytokines, CMV-related mucosal inflammation may have modulated this patient’s disease trajectory, although causality cannot be inferred from a single case. This case highlights prolonged multi-food FPIES with yolk specificity, emphasizes TARC as a pragmatic biomarker during symptomatic episodes, and provides a hypothesis linking gut immaturity and early-life viral inflammation to delayed oral tolerance.