High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders

Abonia, J. Pablo; Wen, Ting; Stucke, Emily M.; Grotjan, Tommie M.; Griffith, Molly S.; Kemme, Katherine A.; Collins, Margaret H.; Putnam, Philip E.; Franciosi, James P.; Tiehl, Karl F. von; Tinkle, Brad T.; Marsolo, Keith; Martin, Lisa J.; Ware, Stephanie M.; Rothenberg, Marc E.

doi:10.1016/j.jaci.2013.02.030

Cited by 166 publications

(120 citation statements)

References 53 publications

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“…This disease is associated with a variety of mendelian genetic based disorders [41] . The most frequent associations of EoE are with hereditary collagen disorders such as Marfan and Ehlers-Danlos syndromes with an incidence of about 1% [42] . Genetic studies have also identified a number of abnormalities.…”

Section: Genetic Vs Environmental Etiological Factorsmentioning

confidence: 99%

Eosinophilic esophagitis: New insights in pathogenesis and therapy

Guarino

Cicala

Behar

2016

WJGPT

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Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multiorgan involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect. Core tip: Eosinophilic esophagitis is a clinico-pathological entity characterized by esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus. Our manuscript provides a deep description of the disease showing that many efforts have been made in the last decades in understanding REVIEWSubmit a

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Section: Genetic Vs Environmental Etiological Factorsmentioning

confidence: 99%

Eosinophilic esophagitis: New insights in pathogenesis and therapy

Guarino

Cicala

Behar

2016

WJGPT

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“…Esophageal epithelial biopsies obtained from patients who have systemic disorders such as hypereosinophilic syndrome may show these features, as well as patients who have significant eosinophil infiltrates in the mucosa of one or more other sites in the gastrointestinal tract (eosinophilic gastrointestinal disorder) or unrelated diseases such as celiac disease or idiopathic inflammatory bowel disease [1,4,5]. Predisposing conditions include a family history of EoE [28] and a connective tissue disorder characterized by hypermobility [29]. There are no features on hematoxylin and eosin-stained slides that identify subjects with predisposing or associated conditions from those without such history.…”

Section: Differential Diagnosismentioning

confidence: 99%

Histopathology of Eosinophilic Esophagitis

Collins

2014

Dig Dis

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Eosinophilic esophagitis (EoE), a chronic relapsing antigen-driven disease, is associated with characteristic esophageal histopathology, including ≥15 intraepithelial eosinophils in at least one high-power field (HPF), and alterations in the epithelium and subepithelial connective tissue. Currently, the pathologic changes in EoE are characteristic but not pathognomonic: the differential diagnosis includes gastroesophageal reflux disease, proton pump inhibitor-responsive esophageal eosinophilia, EoE with significant eosinophilic inflammation in other parts of the gastrointestinal tract (eosinophilic gastrointestinal disorder), etc. EoE biopsy pathology does not vary according to age, sex, or familial predisposition. Genetic analyses of EoE esophageal biopsies have identified a characteristic transcriptome that includes upregulation of several genes that relate to histopathology, such as periostin, thymic stromal lymphopoietin, and desmoglein. Diagnostic pitfalls include the patchy distribution of the characteristic EoE pathology; examining multiple biopsies increases the disease detection rate. The method used to quantitate eosinophils, including the size of the HPF, influences the diagnostic yield, but excellent interobserver variability is achieved among pathologists who agree to a uniform methodology. Therapy for EoE includes diet-based approaches to eliminate offending antigens, topical steroid therapy, and novel biologic agents including monoclonal antibodies. Following appropriate therapy, biopsies may revert to normal histology, but signs and symptoms of esophageal dysfunction may persist. A potential explanation is that endoscopic biopsies obtain very small superficial fragments of tissue from an organ that has complex underlying neuromuscular components; unseen pathology in those loci may influence the clinical state of patients with normal epithelial biopsies.

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“…An eightfold risk of EoE was identified in patients with a CTD [61]. The CTD spectrum includes those with clinically defined genetic etiologies such as Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome.…”

Section: Genetic Variants In Eoe Susceptibilitymentioning

confidence: 99%

“…Moreover, the difficulty (and differences in clinical practices) in distinguishing EoE from other related disorders, namely gastroesophageal reflux disease, could hamper large population genetic studies wherein the success relies on a homogenous, well-phenotyped case cohort. In addition, as several subphenotypes [71] and comorbidities [61,72] in EoE have emerged, identifying the true genetic causality in EoE has been further complicated.…”

Section: Challenges To Eoe Genetic Studiesmentioning

confidence: 99%

Genetics of Eosinophilic Esophagitis

Sherrill

Blanchard

2014

Dig Dis

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Eosinophilic esophagitis (EoE) is a complex genetic disorder characterized by eosinophilic inflammation within the esophagus. Multiple epidemiological studies estimate the prevalence of EoE is 4 in 10,000, with a higher disease prevalence in individuals of European ancestry and in males, highlighting a genetic etiology of the disease. EoE has often been noted to occur in multiple family members, particularly siblings, in a non-Mendelian pattern, indicating the heritable component of EoE is likely complex in nature. Although EoE is a newly diagnosed disorder involving a complex polygenic etiology, much progress has been made towards identifying the molecular pathways contributing to the disease pathogenesis and the genetic variants associated with disease susceptibility using a variety of approaches (genome-wide and candidate gene) as well as study designs (case-control and family-based cohorts). Here, we discuss the major scientific findings that have shaped the current molecular and genetic landscape of EoE as well as the major obstacles in the discovery of disease causal variants in complex disorders.

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High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders

Cited by 166 publications

References 53 publications

Eosinophilic esophagitis: New insights in pathogenesis and therapy

Eosinophilic esophagitis: New insights in pathogenesis and therapy

Histopathology of Eosinophilic Esophagitis

Genetics of Eosinophilic Esophagitis

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