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Eosinophilic Gastrointestinal Disorders Clinical Reviews in Allergy & Immunology (2019) 57:272–285 https://doi.org/10.1007/s12016-019-08732-1 Eosinophilic Gastrointestinal Disorders Nirmala Gonsalves1 Published online:22 March 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Eosinophilic gastrointestinal disorders (EGID) are a group of disorders characterized by pathologic eosinophilic infiltration of the esophagus, stomach, small intestine, or colon leading to organ dysfunction and clinical symptoms (J Pediatr Gastroenterol Nutr; Spergel et al., 52: 300–306, 2011). These disorders include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosino- philic gastroenteritis (EGE), eosinophilic enteritis (EE), and eosinophilic colitis (EC). Symptoms are dependent not only on the location (organ) as well as extent (layer invasion of the bowel wall). Common symptoms of EoE include dysphagia and food impaction in adults and heartburn, abdominal pain, and vomiting in children. Common symptoms of the other EGIDs include abdominal pain, nausea, vomiting, early satiety, diarrhea, and weight loss. These disorders are considered immune-mediated chronic inflammatory disorders with strong links to food allergen triggers. Treatment strategies focus on either medical or dietary therapy. These options include not only controlling symptoms and bowel inflammation but also on identifying potential food triggers. This chapter will focus on the clinical presentation, pathophysiology, and treatment of these increasingly recognized disorders. Keywords Eosinophilic gastroenteritis . Eosinophilic gastritis . Eosinophilic esophagitis . Dysphagia . Food impaction . Food allergy Introduction purpose of this chapter, we will discuss these disorders sepa- rately and focus on the available data on the clinical presenta- Eosinophilic gastrointestinal disorders (EGID) are a group of tion, pathophysiology, and treatment. disorders characterized by pathologic eosinophilic infiltration of the esophagus, stomach, small intestine, or colon leading to organ dysfunction and clinical symptoms [1]. Nomenclature Eosinophilic Esophagitis and the specific presentation of EGID depend on the location (organ) and extent (layer invasion) of eosinophilic infiltration. Background and Epidemiology and Pathophysiology In eosinophilic esophagitis (EoE), the most common of these disorders, eosinophils are isolated to the esophagus. Other less Eosinophilic esophagitis (EoE) is an immune-mediated anti- common disorders include eosinophilic gastritis (EG) where gen-driven disease characterized by pathologic eosinophilic eosinophils are isolated to the stomach. If eosinophils are lo- inflammation of the esophagus as well as esophageal dysfunc- cated more diffusely (esophagus, stomach, and/or small intes- tion leading to clinical symptoms [3]. Over the last decade, tine), we label the illness, eosinophilic gastroenteritis (EGE). EoE has become increasingly recognized as an important dis- Eosinophilic involvement isolated solely to the intestine or ease by allergists, internists, pediatricians, pathologists, and colon is labeled eosinophilic enteritis and colitis (EC) respec- gastroenterologists caring for both pediatric and adult patients. tively. Eosinophils may infiltrate the mucosal layer, the mus- Previously considered a rare condition, there has been a dra- cular layer, or the subserosal layer of the GI tract [2]. For the matic increase in reports of EoE from many continents includ- ing North and South America, Europe, Asia, Australia, and the Middle East. The cause for this rise is thought to be mul- * Nirmala Gonsalves [email protected] tifactorial including a true increasing incidence of EoE in ad- dition to a growing awareness of the condition among clini- 1 Feinberg School of Medicine, Northwestern University, 676 N St. cians [4, 5]. Prior studies have suggested an incidence in chil- Claire St, Suite 1400, Chicago, IL 60614, USA dren to be 10.4 in 10,000 and 3 per 10,000 in adults [6–8]. Clinic Rev Allerg Immunol (2019) 57:272–285 273 These numbers are likely to underestimate the true incidence called eotaxin-3, a gene encoding an eosinophil-specific and prevalence of EoE in the general population since these chemoattractant [18]. Pathophysiology of these interesting studies evaluated patients with symptoms warranting upper disorders is thought to be multifactorial including involve- endoscopy. Esophageal eosinophilia may be more prevalent ment of food and environmental allergens, acid interplay, than this as demonstrated by a population-based study in and genetic factors described above. Sweden which randomly surveyed 3000 adults, 1000 of whom underwent endoscopy with esophageal biopsies. This group found that histologic eosinophilia meeting their criteria Clinical Features for definite and probable EoE was present in 1% of the pop- ulation [9]. These numbers suggest that incidence of EoE may As with other diseases, some age-related differences in clinical one day approximate that of other immunologically driven presentation are noted between children and adults [19, 20]. disorders such as inflammatory bowel disease. This increase The most common presenting symptoms in adults include also reflects the rising trends in other immunologically driven dysphagia, food impaction, heartburn, and chest pain with disorders such as asthma, atopy, and food allergies [10]. one study showing as many as 50% of adult patients with food Eosinophilic esophagitis has a male predilection. Results impaction were diagnosed with EoE [3]. from 323 adult patients from 13 studies observed that 76% Children present differently however with the most com- were males with a mean age of 38 years (range 14 to 89 years). mon complaints being vomiting, heartburn, regurgitation, Results from 754 pediatric patients from 16 studies found that emesis, and abdominal pain [14, 21]. While younger children 66% were male with a mean age of 8.6 years (range 0.5 to rarely present with dysphagia and food impaction typical of 21.1 years) [3, 11]. While most studies show a Caucasian adult complaints, these presentations were more often seen in predilection, EoE has been described in patients with varied older children and adolescents [6]. In adults, there has been a ethnicities including those African American, Latin- delay of diagnosis with prior misdiagnosis of alternate diag- American, and Asian descent [11]. In a case-control study that noses, including Schatzki rings or gastroesophageal reflux included 115 patients with EoE and 225 controls, patients with disease (GERD) [22]. In many cases, these patients had un- EoE were significantly less likely to have smoked cigarettes or dergone repeated endoscopies, esophageal dilations, and a de- actively use NSAIDs (OR 0.36 and 0.47, respectively) [12]. lay in the institution of appropriate medical therapy. One rea- However, there was no significant difference in rates of son for the delay of diagnosis could be that prior literature in smoking or NSAID exposure between cases with or without the pathology community equated the presence of eosinophils fibrostenosing disease or among patients with a post-treatment in esophageal mucosal biopsies with GERD and therefore histologic response. More recent studies have suggested that some specimens may have been classified as reflux. Due to early-life factors, including maternal fever, preterm labor, ce- this potential overlap, gastroenterologists who suspect a diag- sarean delivery, and antibiotic or acid suppressant use in in- nosis of EoE should specifically request tissue eosinophil fancy, were associated with risk of pediatric EoE. counts as well as description of other inflammatory features Interestingly, having a pet in the home was protective. These to help differentiate this diagnosis from GERD. Recent inves- results implicate early-life exposures in EoE pathogenesis and tigations by prominent eosinophil pathologists are now are being further investigated [13]. looking at a newer histologic scoring system which takes into account additional inflammatory features rather than focusing Genetics solely on the eosinophil number [23]. A familial pattern has been recognized in both the adult and Endoscopic Findings pediatric population. In a case series of 381 children with EoE, 5% of patients had siblings with EoE and 7% had a parent Patients with eosinophilic esophagitis have characteristic fea- with either an esophageal stricture or a known diagnosis of tures on endoscopy suggestive of the diagnosis. The most EoE [14–16]. Therefore, a workup of patients should include a common endoscopic features in adults with EoE include linear thorough family history [12]. or longitudinal furrows (80%), mucosal rings (64%), small A genetic predisposition to EoE is supported by evidence caliber esophagus (28%), white plaques and/or exudates of familial clustering and twin studies, which have revealed a (16%), and strictures (12%) [24](Fig.1). In a large clinical 58% concordance in monozygotic twins and a 36% concor- series of 381 children, the most common endoscopic features dance in dizygotic twins compared with regular fraternal sib- were linear furrows (41%), normal appearance (32%), esoph- lings [17]. In addition, several genetic variants that may pre- ageal rings (12%), and white plaques (15%) [14, 21]. While dispose to EoE have been identified, especially at 5q22 (TSLP these are the characteristic features, they can often be subtle gene) and 2p23 (CAPN14 gene) as well as a genome-wide and missed on endoscopy, so it is
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