ABSTRACT
BACKGROUND & AIMS: Eosinophilic esophagitis (EE) occurs in families. METHODS: Record review confirmed patient kinship and provided clinical information. Slide review confirmed the diagnosis (threshold peak number > or = 24 eosinophils/high-power field). RESULTS: Fifty-nine members (41 males, 18 females) of 26 families were 3 months to 47 years of age (mean age, 10.3 y) at diagnosis. The only recorded race was Caucasian. In 4 families a parent of an affected male had EE. The most common complaint at diagnosis was dysphagia (68% of patients). Endoscopy showed esophageal mucosal furrows (93% of patients) and exudates (44%). Fifty-one percent had asthma. Skin prick tests to food and aeroallergens were positive in 76% and 71%, respectively. Familial EE characteristics (clinical, endoscopic, pathologic, and global esophageal transcript expression profile analysis) were similar to sporadic EE, except among patients with mucosal furrows: familial patients had lower peak eosinophil counts in the distal esophagus (P = .03) compared with sporadic patients. The basic characteristics of EE (eg, eosinophil levels, rate of atopy) did not vary with patient age. By using genome-wide microarray analysis, no significant differences (P < .05, false-discovery rate) were observed between familial and sporadic EE. Among all patients, chest pain was more common in females (P = .02), and thickened mucosa was more common in males (P = .006). CONCLUSIONS: These data support a familial pattern of inheritance of EE and a pathogenesis shared with sporadic EE. EE should be considered in symptomatic family members of patients who have EE.
Subject(s)
Eosinophils/immunology , Esophagitis/pathology , Esophagitis/physiopathology , Family Health , Adolescent , Adult , Asthma , Child , Child, Preschool , Deglutition Disorders/etiology , Esophagitis/genetics , Esophagitis/immunology , Esophagoscopy , Female , Gene Expression Profiling , Humans , Infant , Male , Middle Aged , Mucous Membrane/pathology , Oligonucleotide Array Sequence Analysis , White PeopleABSTRACT
BACKGROUND: Eosinophilic esophagitis (EE) is a gastrointestinal disorder that is increasingly diagnosed in pediatric patients. OBJECTIVE: We aimed to define, in pediatric patients with EE, their demographic and atopic characteristics, the histopathology of all segments of the gastrointestinal tract, and the effect of therapeutic interventions on the natural history. METHODS: We conducted a retrospective analysis of a database of pediatric patients with EE followed over a period of 8 years. RESULTS: In 89 pediatric patients with EE, male sex (78.6%), white race (94.4%), young age at diagnosis, mean +/- SD, 6.2 +/- 4.8 years, and atopy with sensitization to environmental and food allergens in 79% and 75%, respectively, were prevalent. Patients had EE of the proximal and distal esophagus, and 77% had in addition either mucosal eosinophilia or noneosinophilic histopathology in the stomach, duodenum, and colon. EE was chronic, with a duration of mean +/- SD, 0.91 +/- 0.84 years, until first resolution, and was recurrent; of 66% of the patients who had resolution, 79% later relapsed. CONCLUSION: Eosinophilic esophagitis in the pediatric population is a chronic and relapsing condition, associated with atopy and sometimes with subsequent histopathology in segments of the gastrointestinal tract other than the esophagus. CLINICAL IMPLICATIONS: Physicians evaluating pediatric patients with chronic gastrointestinal symptoms should consider the diagnosis of EE, particularly in young white male patients with atopy. Once diagnosed and treated, the physicians should follow the patients over a period of several years because the course of the disease is protracted, other gastrointestinal segments may be affected, and relapses are common.
Subject(s)
Eosinophilia/diagnosis , Esophagitis/diagnosis , Hypersensitivity, Immediate/diagnosis , Adolescent , Child , Child, Preschool , Colon/pathology , Duodenum/pathology , Endoscopy , Esophagitis/immunology , Esophagitis/therapy , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Stomach/pathologyABSTRACT
BACKGROUND & AIMS: Eosinophilic esophagitis is an increasingly recognized disorder with distinctive endoscopic, histologic, and allergic features. Although several therapies are advocated, no placebo-controlled trials have been conducted. We aimed to determine the efficacy of swallowed fluticasone propionate (FP) in the treatment of eosinophilic esophagitis. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of swallowed FP in pediatric patients with active eosinophilic esophagitis. Thirty-six patients were randomly assigned to receive either 880 mug of FP (21 patients) or placebo (15 patients) divided twice daily for 3 months. The primary end point was histologic remission, defined by a peak eosinophil count of
Subject(s)
Androstadienes/therapeutic use , Eosinophilia/drug therapy , Esophagitis/drug therapy , Adolescent , Age Factors , Body Height , Body Weight , CD8-Positive T-Lymphocytes/immunology , Child , Child, Preschool , Double-Blind Method , Eosinophilia/immunology , Eosinophilia/pathology , Esophagitis/immunology , Esophagitis/pathology , Female , Fluticasone , Humans , Hyperplasia , Infant , MaleABSTRACT
BACKGROUND & AIMS: Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. METHODS: A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. RESULTS: AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/muL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. CONCLUSIONS: These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.
Subject(s)
Biomarkers/blood , Chemokines, CC/blood , Eosinophil-Derived Neurotoxin/blood , Eosinophilia/diagnosis , Eosinophils , Esophagitis/diagnosis , Immunologic Factors/blood , Leukocyte Count , Adolescent , Chemokine CCL26 , Child , Child, Preschool , Cross-Sectional Studies , Eosinophilia/blood , Esophagitis/blood , Female , Humans , Infant , Male , Prospective Studies , ROC Curve , Sensitivity and SpecificityABSTRACT
Calprotectin is an abundant neutrophil protein found in both plasma and stool that is markedly elevated in infectious and inflammatory conditions, including inflammatory bowel disease (IBD). We conducted a systematic review of the published literature regarding fecal calprotectin to evaluate its potential as a noninvasive marker of neutrophilic intestinal inflammation. Reference ranges for fecal calprotectin have been established in healthy adults and children, and elevated concentrations of fecal calprotectin have been demonstrated in numerous studies of patients with IBD. Fecal calprotectin correlates well with histological inflammation as detected by colonoscopy with biopsies and has been shown successfully to predict relapses and detect pouchitis in patients with IBD. Fecal calprotectin has been shown to consistently differentiate IBD from irritable bowel syndrome because it has excellent negative predictive value in ruling out IBD in undiagnosed, symptomatic patients. Fecal calprotectin also may be useful in determining whether clinical symptoms in patients with known IBD are caused by disease flares or noninflammatory complications/underlying irritable bowel syndrome and in providing objective evidence of response to treatment. Although more studies are needed to define fully the role of fecal calprotectin, convincing studies and growing clinical experience point to an expanded role in the diagnosis and management of IBD.
Subject(s)
Feces/chemistry , Inflammatory Bowel Diseases/diagnosis , Leukocyte L1 Antigen Complex/analysis , Biomarkers , Colonic Pouches/pathology , Diarrhea , Enzyme-Linked Immunosorbent Assay , Humans , Inflammatory Bowel Diseases/therapy , Intestinal Diseases/diagnosis , Recurrence , Sensitivity and SpecificityABSTRACT
Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis.
