**1. Introduction**

Cow's milk allergy (CMA) is the most common allergy in the first year of life. It takes two forms: the IgE-mediated CMA (IgE-CMA) and the non-IgE mediated CMA (non-IgE-CMA). Non-IgE-CMA is characterized by digestive symptoms and has a good prognosis, usually resolving before the age of three. In contrast to IgE-CMA, the diagnosis of various non-IgE-CMA syndromes can be challenging due to the overall lack of noninvasive confirmatory testing for these disorders. Many of the non-IgE-CMA syndromes are diagnosed clinically based on history, diagnostic milk-free diet, and followed by positive milk provocation test, which is a "gold standard" for diagnosing these diseases [1,2].

The first classification of non-IgE-CMA gastrointestinal disorders was proposed by Sampson HA in 2003 [3]. The classification was adopted by WAO in 2010 (DRACMA) and EAACI in 2014. [4,5]. It covers three items: food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy syndrome (FPIE) as well as the syndrome of eosinophilic gastrointestinal diseases (EGID), where milk can cause allergic reactions under the IgE-dependent and IgE-independent mechanism.

FPIES is a non-IgE cell-mediated food allergy [6]. The first international consensus on these diseases was published in 2017 by an international workgroup convened through the Adverse Reactions to Foods Committee of the AAAAI and the International

**Citation:** Bulsa, K.; Standowicz, M.; Baryła-Pankiewicz, E.; Czaja-Bulsa, G. Chronic Milk-Dependent Food Protein-Induced Enterocolitis Syndrome in Children from West Pomerania Region. *Nutrients* **2021**, *13*, 4137. https://doi.org/10.3390/ nu13114137

Academic Editor: Carla Mastrorilli

Received: 3 October 2021 Accepted: 17 November 2021 Published: 19 November 2021

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FPIES Association advocacy group [7]. Previously, diagnosis had been made based on descriptions [8,9].

FPIES usually manifests with repeated vomiting, and less commonly with watery diarrhea, often accompanied by lethargy and pallor. Severe cases can lead to dehydration with ionic disturbances, acidosis, methemoglobinemia, and hypotension (in at least 15% of reactions) mimicking sepsis. Delayed onset (1–4 h after food ingestion) and absence of cutaneous and respiratory symptoms suggest a systemic reaction different from anaphylaxis [7].

FPIES is a syndrome that occurs in two forms, acute and chronic. The acute form of FPIES is much more severe and is caused by food ingested intermittently or after a period of avoidance (solid foods); therefore, it occurs in infants no sooner than after the introduction of modified diet, i.e., usually after 6 months of life. The foods that most commonly cause acute FPIES are rice and oat, which account for almost <sup>1</sup>/<sup>3</sup> of cases in the USA and Australia [9–11]. In 2009, Mehr et al. highlighted the emerging importance of rice, a food commonly thought to be "hypoallergenic", which cause severe FPIES [11]. In Spain and Italy, FPIES is often caused by a fish-based diet, which is rare in other countries [7,12,13]. Other foods more likely to cause FPIES symptoms include corn, peas, poultry, egg, and goat milk [7].

The chronic form of FPIES is caused by regularly administered food, typically milk or soy infant formula. It is reported only in infants younger than 4 months of age, usually shortly after the end of breastfeeding (2–3 weeks). The main symptoms of chronic FPIES are intermittent vomiting and watery diarrhea rapidly leading to weight and growth deficits. Severe type of chronic FPIES can lead to dehydration and hypoalbuminemia. During the food oral challenge an acute reaction always occurs in the following order: first vomiting (after 1–4 h of food ingestion) followed by watery diarrhea (after 5–10 h of food ingestion). This acute symptomatology during the oral challenge after food avoidance is typical for chronical FPIES. It is also the basis for distinguishing chronic FPIES from FPIE and eosinophilic gastroenteritis [1,7].

The purpose of the study was to describe chronic milk-dependent FPIES (chronic milk-FPIES) in children from the region of Western Pomerania who were diagnosed over a 5-year period (2014–2018).
