**3. Results**

Chronic FPIES after consumption of cow's milk proteins was diagnosed in 55 children in median age of 2.2 months (1.6–2.6 months) (Table 1). It was the age at which the diagnostic milk-free diet began. Symptoms of CMA appeared after cessation of breastfeeding and introduction of milk formula (80% of children) or mixed feeding (20% of children). After 2–4 weeks of CMA symptoms, a milk-free diet was started. Vomiting and diarrhea escalated gradually but quickly led to physical retardation.

**Table 1.** Characteristics of children from the study group with chronic food protein-induced enterocolitis syndrome (FPIES) dependent on cow's milk protein intake in the study group of children.


\* BMI—body mass index; c—percentile; \*\* SPT—skin prick test; \*\*\* OFC—oral food challenge.

At the time of diagnosis as many as half of infants (49%) had low BMI < 10 c (Table 1). In every fifth child it was extremely low at BMI ≤ 3 c. A quarter of the children had iron deficiency anemia and 15% of the children suffered from hypoalbuminemia.

All 55 children with chronic milk-FPIES were affected by the recurrent vomiting, bloating, and diarrhea, sometimes with mucous (42%) and blood in stools (31%) (Table 1). Their weight gain was poor.

The first milk OFC (1. OFC) was performed in children in median age of 3.6 months (2.1–5.5 months). Vomiting (after 2–3 h), diarrhea (after 4–10 h), and pallor were observed in all children (Table 1). As many as 42% of children required intravenous hydration and 7% received ondansetron. Their blood tests revealed increased white blood cell count and neutrophilia in 80% of children. There was no eosinophilia. No child had acidosis or methemoglobinemia. After the diagnosis of chronic milk-FPIES was made, parents were informed that the supply of milk or milk products to their children should only be attempted under medical supervision. The supply of these foods at home can be dangerous.

A family history of atopy was reported in 64% of children (mother—52%, father—58% or siblings—29%) (Table 1). At the time of diagnosis of chronic milk-FPIES, 18% of the children also had atopic dermatitis (AD).

Lactose-free casein hydrolysates (eHF) and AFF were used in treatment of children with chronic milk-FPIES. AFF was administered to 11 children (20%) who were diagnosed with severe CMA type (BMI ≤ 3 c). Resolution of allergy symptoms and improvement in health were observed in all infants already after 3–14 days of dietary treatment.

In every fourth child the elevated sIgE and positive SPT for cow's milk proteins were found (Table 1). Typically, sIgE values were low, in the range of 0.35–0.7 kU/L, rarely higher (2.8, 3.9, 6.9, 28.3 kU/L) and they decreased in the next tests. At the time of chronic milk-FPIES diagnosis no immediate reactions after milk consumption were observed. Immediate symptoms after milk ingestion (IgE-dependent CMA) were seen in 3 children (5.5%) during the subsequent challenge trials (at 19, 25, and 26 months of age) (Table 2). During the provocation, those children developed extensive urticaria, with two of them also suffering from bronchospasm. At that time no symptoms of chronic milk-FPIES were seen in those children. In the following years, their milk sIgE levels increased. Due to lack of parental consent, we could not perform control provocations during 3 years of observation.

Apart from allergy to milk, 10 children (18%) had positive results of SPTs to other foods (egg white, wheat, corn, banana, soybean, peanut), in some cases up to 4 positive SPTs in one child (Table 1). When these foods were first introduced to the diet, two infants developed symptoms of IgE-dependent allergies. One child presented mild urticaria about 30 min after egg white ingestion (at 8 months of age), while second (after 6 months of age)—after wheat intake (Table 3).
