A 25-day-old male neonate was transferred to an emergency unit due to lethargy with general cyanosis since this morning. He was born at 39⁺³ weeks of gestation with a birth weight of 3,500 g (50th-75th percentile). He was formula-fed from birth. Beginning 7 days ago, he was presented with vomiting (2-3 times/day) and mucous and loose stool (5-6 times/day). Mild fever developed 2 days ago. Last night, weak sucking power with a sleepy condition developed. No family history of food allergy was recorded. His body weight was 2,850 g (<3rd percentile). He was drowsy and appeared malnourished and chronically ill with sepsis-like manifestation. Facial and truncal cyanosis, dried oral mucosa, and abdominal distention without hepatosplenomagaly were observed. Heart beat was weak, but without murmur, and lung sounds were relatively clear. Laboratory tests revealed peripheral blood leukocytosis with a shift to left (18% band form), thrombocytosis, hypoalbuminemia, and metobolic acidosis. Methemoglobinemia (positive ≥15%) was 25%. The results of a renal function test, serum ammonia level, serum and urine amino acid analysis, and serum immunoglobulins and T cell subsets were within normal ranges. The UniCAP test for milk was class 0. Abdominal roentgenography revealed pneumatosis intestinalis in the bowels. Gastrofiberscopy and duodenal mucosal biopsy revealed subtotal villous atrophy but without eosinophilic infiltrations. No pathogens were detected in the blood, urine, and stool cultures. The result of rectal suction biopsy was incompatible with Hirschsprung's disease. Abdominal ultrasonography showed portal venous gas. Necrotizing enterocolitis (NEC) was confirmed even though he was not a preterm baby. After methylene blue and bicarbonate injections, treatment with total parenteral nutrition, broad spectrum antibiotics, and albumin supplements was maintained for 7 days. When he was in a relatively stable condition, the open OFC test with cow's milk formula (0.15 g milk protein/kg) was performed to evaluate for possible FPIES. Baseline complete blood count with a differential was obtained before the starting of feeding. Two hours after the feeding, colic irritability with repetitive, projectile vomiting developed. Three hours of feeding, lethargy with pallor occurred, and blood pressure was 65/38 mmHg. Normal saline (30 mL/kg for 1 hour) and dextrose saline were given intravenously. Two hours after the fluid therapy, his general condition improved to a relatively active condition. Six hours after the feeding, absolute neutrophil count of peripheral blood was elevated to 5,600 cells/mm³ from baseline (positive >3,500 cells/mm³). Seven hours later, pus-like and foul-odored loose stool was observed. After 8 hours, he was fed an extensively hydrolysate formula (eHF), and no vomiting or adverse symptoms were observed. Although loose stools were observed, he recovered to be active and stable 24 hours after the OFC. He was conclusively diagnosed with FPIES [16].

The patient was fed eHF and maintained on a strict milk protein elimination diet until 6 months of age. Then, solid foods were serially and carefully introduced under a physician's supervision, but no adverse reaction developed. At 10 months of age, OFC with soy-based formula was performed, and no reaction was observed. The eHF was changed to soy formula. At 12 months of age, OFC with cow's milk formula was performed, and repetitive vomiting and pallor occurred. At 18 months of age, he outgrew the milk intolerance and was freely fed all foods without any adverse symptoms of FPIES. Other allergic diseases (e.g., urticaria, atopic dermatitis, asthma, and allergic rhinitis) have not been observed in adolescence.

Typical FPIES, milk FPIES, early onset, chronic symptom, sepsis-like symptoms and failure to thrive, NEC induced by food allergy [10,16,17].

A 6-month-old boy, exclusively breastfed, was admitted to emergency unit with repetitive and profuse vomiting (over 10 times/hour), cyanosis, and lethargy within 4 hours after first consuming approximately 30 mL of milk formula. Four weeks previously, a similar clinical situation occurred episode after ingesting milk formula. At that time, physicians at emergency unit diagnosed him with acute viral gastroenteritis. A history revealed a common clinical feature between the two episodes; 1.5-2 hours after feeding, irritability followed by repetitive, projectile vomiting occurred. After 2 hours, a lethargic condition with ashen-gray appearance developed. Blood pressure was 65-70/42-45 mmHg. Normal saline and subsequent dextrose saline were given intravenously. Three hours after fluid therapy, his general condition improved to be relatively active. Seven hours after feeding, a mucous and bloody loose stool was observed. He was refed with breast milk, and no vomiting was observed. Twelve hours after the feeding, although a few loose stools were observed, he was completely recovered to be active and stable. The result of the UniCAP test for milk was class 0. The clinical history of two episodes with acute adverse symptoms after feeding cow's milk was compatible with the diagnostic criteria of FPIES [5,6]; therefore, he was conclusively diagnosed with FPIES.

He was breastfed with an eHF supplement and maintained on strict milk protein avoidance until 10 months of age. Solid foods were serially introduced under a physician's supervision, but no adverse reaction occurred. At 10 months of age, OFC with soy-based formula was done and no reaction was observed. At 12 months of age, OFC with milk formula was performed and repetitive vomiting with cyanosis developed. At 15 months of age, he had outgrown the milk intolerance and could eat all foods without any adverse reactions. No other allergic diseases have been observed in adolescence.

Typical FPIES, milk FPIES, late onset, acute reaction, acute gastroenteritis-like clinical feature [10,18].

A 6-month-old girl was admitted to the inpatient unit with projectile vomiting and lethargy after consuming about 20 mL of rice gruel at the start of a weaning diet. She was formula-fed from birth without any adverse symptoms. Four weeks later, an open OFC was performed with rice gruel in the inpatient unit. After feeding rice, she developed projectile vomiting, pallor with lethargy, and diarrhea. These serial symptoms and their timing were consistent with FPIES [5,6]. The result of rice-specific UniCAP test was negative.

Thereafter, she manifested with no adverse reaction to almost all foods appropriate for her age, but after accidentally eating rice gruel at 10 months, she was presented again with symptoms of repetitive vomiting with lethargy. However, none of the allergic symptoms were demonstrated at 15 months of age after a follow-up OFC with rice gruel. No other allergic diseases have been observed in late childhood.

Typical FPIES, solid food-FPIES, late onset, acute reaction, acute gastroenteritis-like symptom [19,20]