Eosinophilic gastrointestinal diseases (EGIDs) are divided into two main groups: eosinophilic esophagitis (EoE) and eosinophilic gastroenteropathies (EGE).
EoE, the most common form of EGID, is a chronic inflammatory disease confined to the esophagus, with a presumed immune-allergic pathogenesis, characterized by alternating periods of clinical remission and episodes of disease activity. From a histological standpoint, it is defined by marked mucosal eosinophilia (>15 eosinophils per high-power field [HPF] in proximal, mid, and distal esophageal biopsies) and by symptoms secondary to esophageal dysfunction.
The annual incidence of the disease varies depending on the geographic origin of the population studied, ranging from 1.6 new cases per 100,000 children per year in Denmark to 8 in the United Kingdom, and from 0.7 to 10 in the United States.
EoE should be suspected in the presence of chronic symptoms of esophageal dysfunction and/or fibrosis that do not respond to high-dose proton pump inhibitor (PPI) therapy (1 mg/kg/day) administered for 8 to 12 weeks.
As for clinical presentation, infants and preschool children often show feeding difficulties, with symptoms that largely overlap with those of gastroesophageal reflux disease (GERD), whereas school-age children more commonly present with vomiting or pain-related symptoms. Dysphagia, on the other hand, is the predominant symptom in adolescents and adults.
Between 40% and 90% of children with EoE have signs and/or symptoms of atopy, such as asthma, allergic rhinitis, or atopic dermatitis. This finding, together with a family history of atopy—which is also reported in a high proportion of cases—can be helpful in supporting the diagnosis.
EGE, by contrast, comprise a group of rare, heterogeneous, and still poorly defined disorders, both clinically and in terms of their underlying pathogenesis. They are diagnosed when eosinophilic infiltration is found in one or more parts of the gastrointestinal tract in the absence of a known cause of eosinophilia. Reported prevalence varies across geographic regions, with rates ranging from 0.2 to 5 cases per 100,000 children in the United Kingdom, to 8.9 cases in Australia, and up to 43 cases per 100,000 children in the United States.
Diagnosis is generally based on three main criteria:
The clinical presentation of EGE varies according to the segment of the gastrointestinal tract involved, but the most common manifestations include vomiting, diarrhea, abdominal pain, weight loss or failure to thrive due to malabsorption and protein loss, overt or occult bleeding, anemia, and obstructive jaundice.
EGE may then be classified either according to the intestinal segment involved, such as gastritis, gastroenteritis, colitis, or proctocolitis, or according to the tissue layer in which eosinophils are predominantly located, namely serosal, mucosal, or muscular. The mucosal form is the most common, while the muscular form is the rarest. Given the rarity of these disorders, before making a diagnosis of EGE, more common causes of tissue eosinophilia must be ruled out, including parasitic infections, inflammatory bowel disease, connective tissue disorders, drug allergy, and lymphoproliferative disorders.
When the muscular layers are involved, abdominal pain, cramping, and intestinal obstruction may be the presenting symptoms, and in rare cases organ perforation may occur. Serosal forms are associated with ascites and abdominal distension.
Epidemiology
EGE has an estimated prevalence of 1–5 per 100,000 and belongs to the group of eosinophil-associated gastrointestinal disorders. It can affect all age groups, with a mean age at presentation between 30 and 50 years, and shows a slight male predominance. The highest prevalence appears to be reported in North America, Sweden, and Australia, with an incidence of approximately 5–7 per 100,000 inhabitants and a prevalence of 50–60 per 100,000 inhabitants. In Europe, the main data come from Switzerland, where the estimated prevalence is around 23 per 100,000 inhabitants. A recent Canadian population-based study found an increase in EoE incidence from 2.1 to 11.0 per 100,000 people. This trend may partly reflect the growing number of esophageal biopsies being performed, although endoscopic procedures for dysphagia also appear to have increased over time. The male-to-female ratio is estimated to be 3:1, although there is currently no clear pathophysiological explanation for this finding. White Americans appear to be more frequently affected (58%) than African Americans (34%) and other ethnic groups (8%).
The diagnosis of EGE is based on three main clinical criteria, which apply across all age groups:
According to the guidelines of the Italian Society of Gastroenterology (SIGE), the diagnosis of EoE is defined by the following criteria:
EGE should be suspected in individuals with chronic and/or recurrent gastrointestinal symptoms, usually occurring in episodes lasting 2 to 4 weeks. Symptoms vary depending on the segment of the gastrointestinal tract involved. When the stomach is affected, dyspeptic symptoms are usually present. When the small intestine is involved, abdominal pain, diarrhea, and bloating are commonly reported. In general, symptoms are worsened by meals and are often associated with weight loss. In some cases, signs such as malabsorption with steatorrhea, iron-deficiency anemia, protein-losing enteropathy, ascites with a high eosinophil count, and even intestinal obstruction may occur. Visible blood in the stool or a positive fecal occult blood test may also be found, and approximately 50% of patients may have associated atopic conditions. Peripheral hypereosinophilia, along with conditions such as asthma, allergic rhinitis, and atopic dermatitis, should raise suspicion of EGE in the presence of chronic gastrointestinal symptoms.
EoE should be suspected on the basis of symptoms, which may vary according to the patient’s age. In infants and young children, signs may include poor growth, increasing feeding difficulties up to complete food refusal, nausea, vomiting, and abdominal pain. In adults and in older children and adolescents, the most common symptoms are dysphagia, food bolus impaction, delayed passage of food, retrosternal heartburn, regurgitation, vomiting, chest pain, and odynophagia. Suspicion may also arise when endoscopy shows typical esophageal findings such as concentric rings, vertical furrows, whitish exudates, edema, and strictures.
After specialist evaluation for suspected EoE or EGE, the patient should be referred to the dedicated diagnostic and care pathway center, where, depending on the complexity of the case, management may take place on an outpatient basis or within a day hospital or inpatient setting, under the care of the facility’s multidisciplinary team.
In addition to essential professionals such as the gastroenterologist or pediatrician, the team involved in patient management should also include the following specialists:
Treatment of EGE is not supported by strong scientific evidence and is therefore largely empirical and based on disease severity. Some authors have suggested that therapeutic goals should include not only symptom reduction, but also a reduction of more than 50% in peripheral eosinophilia, when present, and, where possible, a reduction in tissue eosinophilia.
In EoE, the therapeutic target is defined as reducing the number of eosinophils in esophageal biopsies to fewer than 15/HPF, together with improvement in symptoms after 6 to 12 weeks of treatment. In children, treatment must also ensure normal growth and development. In pediatric patients, where symptoms are mainly driven by inflammation rather than fibrosis, medical treatment alone may be sufficient to improve symptoms. In adults, however, the presence of strictures may make endoscopic dilation necessary.
The nutritional therapies proposed for the treatment of EGE and EoE are essentially of three types: an elemental diet based on amino acid formula; an oligoantigenic diet based on the empirical removal of certain classes of foods, known as the six-food elimination diet; and a diet guided by positive allergy test results. A dietary approach lasting 6 weeks may be considered a first-line treatment in mild disease. In adult patients, both a top-down dietary strategy—starting with elimination of six foods followed by gradual reintroduction of one food class at a time, with endoscopic and histological reassessment to identify trigger allergens—and a step-up strategy—initially eliminating two foods, preferably cow’s milk proteins and gluten/wheat, and then further restricting the diet if efficacy is not confirmed on endoscopic and histological follow-up—have been explored.
As for diets guided by allergy testing, skin prick tests, measurement of specific IgE, and atopy patch tests appear to have a limited role, although further studies are needed.
Eosinophilic Esophagitis is clearly associated with allergic mechanisms, and even when routine clinical tests do not explicitly demonstrate them, it has been observed that when patients are placed on an elemental diet based on essential amino acids, the eosinophil count in the esophagus may decrease substantially, in some cases even completely. However, these products are not yet specifically recognized for EoE within the National Health Service.
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