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Histology Scoring System (HSS) is Superior to Peak Eosinophil Count (PEC) to Identify Treated vs Untreated Eosinophilic Esophagitis (EoE) Patients
AB96 Abstracts
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
SUNDAY
363
Histology Scoring System (HSS) is Superior to Peak Eosinophil Count (PEC) to Identify Treated vs Untreated Eosinophilic Esophagitis (EoE) Patients M. H. Collins1, L. J. Martin1, E. S. Alexander1,2, S. Pentiuk1, A. Ellison1, P. E. Putnam1, J. P. Franciosi1, J. P. Abonia1, M. E. Rothenberg1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2University of Cincinnati College of Medicine, Cincinnati, OH. _15 eosinophils per high power field in esophageal RATIONALE: PEC > biopsies is an EOE diagnostic criterion. We hypothesize greater discrimination among EoE biopsies occurs using a HSS including additional pathology (eosinophil abscesses/surface layering, epithelial hyperplasia and necrosis/ apoptosis, dilated intercellular spaces, lamina propria fibrosis). METHODS: Biopsy slides were scored retrospectively using an 8 point HSS to grade (measure severity) and stage (measure prevalence) histologic characteristics. Univariate data were analyzed using two-tailed Student _0.05. Wilcoxon 2-sample nonparametric tests were used to t-tests at p< _0.05. Logistic regression compare HSS parameters by treatment status at p< _0.05) with AICc were used to compare goodness of fit for models (p< models designed to predict treatment status. RESULTS: A total of 46 proximal and 42 distal esophageal biopsies from 41 patients were scored. Demographics were 81%male, 100%white, age 10.1664.53years (range3-18years) without differences between treated (diet and/or topical steroids) (35 endoscopies) vs untreated (11 endoscopies). Using nonparametric tests, PEC in distal (PECD) and proximal (PECP) biopsies, maximum PEC in either site (PECMax), and maximum stage (MSS) and grade (MGS) scores were associated with treatment status (p<0.01). Logistic regression models were significant for PECP and PECMax, and MSS and MGS, but not for PECD. Goodness of fit was superior for both MSS(42.79) and MGS(46.78), compared to PECP and PECMax(50.3,50.4) with MSS having the best fit. CONCLUSIONS: HSS is superior to eosinophil counts to identify EoE biopsies following therapy. HSS more completely evaluates mucosal healing than PEC, and likely forms a better basis for making therapeutic decisions.
Predicting Esophageal Biopsy Eosinophil Counts from Presenting Symptoms in Patients with Suspected Eosinophilic Esophagitis M. J. Greenhawt1, W. Rassbach2, M. Elkins2, J. K. Greenson1; 1The University of Michigan Medical School, Ann Arbor, MI, 2The University of Michigan Health System, Ann Arbor, MI. RATIONALE: Eosinophilic Esophagitis (EoE) is a clinicopathological condition hallmarked by esophageal eosinophilia >15 per high powered field(hpf) on biopsy. EoE symptomatology has considerable overlap with gastroesophageal reflux disease (GERD). No symptom patterns accurately distinguish the conditions without a biopsy. METHODS: Chart review of 504 consecutive pediatric and adult patients who underwent esophageal biopsy between 2008 and 2011. 19 symptoms were analyzed by logistic regression to determine their association with diagnostic cell counts indicative of EoE (> 15/hpf). RESULTS: 78.4% (388/495) had biopsies with diagnostic counts. Pediatric bivariate analysis indicated dysphagia to solids, duration of symptoms >6 months, and Caucasian race positively predicted; but weight loss/failure to thrive, vomiting, and abdominal pain negatively predicted diagnostic counts. On multivariate analysis, dysphagia to solids (OR 2.13, CI95%1.35-3.37, p>0.001) and weight loss (OR 0.406, CI95%0.21-0.784, p>0.007) predicted diagnostic counts. Adult bivariate analysis indicated regurgitation, atopy, and dysphagia to solids positively predicted; but early satiety, nocturnal awakening, weight loss, and reflux/heartburn negatively predicted diagnostic counts. On multivariate analysis, regurgitation (OR 2.29, CI95%1.1-4.74, p>0.025), dysphagia to solids (OR 1.82, CI95%1.13-2.93, p>0.013), early satiety (OR 0.359, CI95%0.14-0.898, p>0.029), weight loss (OR 0.463,CI95%0.0249-0.861, p>0.015) and chest pain (OR 0.55, CI95%0.310.975, p>0.041) predicted diagnostic counts. With multivariate adjustment for PPi use, dysphagia to solids and weight loss in adults remained significant. CONCLUSIONS: Dysphagia to solids positively predicted, and weight loss negatively predictive diagnostic counts in all ages, but after adjustment for PPi use only remained significant in adults. Further prospective study is needed for additional confirmation.
364
366
The Potential Benefit of Immunotherapy in the Treatment of Eosinophilic Esophagitis in Adult Patients S. Silverman, C. Bassett, E. Rothstein; New York University Langone Medical Center, New York, NY. RATIONALE: This study examined 2 groups of adult patients with eosinophilic esophagitis to assess immunotherapy’s possible added treatment benefit. METHODS: This was a retrospective chart review of 12 adult patients with eosinophilic esophagitis, diagnosed by esophageal biopsy. Group A included 6 patients (4 male, 2 female, ages 30-45), all receiving immunotherapy, medications, and diet changes. Group B included 6 patients (4 male, 2 female, ages 30-45), selected from 45 eosinophilic esophagitis patients to match age/gender distribution of Group A, on medications and diet changes alone. All patients were asked to rate symptom severity on a 1-10 scale (15nonexistent, 105most severe). RESULTS: Of Group A, all patients experienced pre-treatment dysphagia (daily to every few months). Pre-treatment symptom severity ranged 2-10/ 10 (average 6/10). All patients started swallowed fluticasone. Five started proton pump inhibitors (PPIs). Five made diet changes. All patients were on immunotherapy to treat seasonal allergies, for a period from 6 months to greater than 2 years. Post-treatment, 2 patients reported their dysphagia had completely resolved. Four reported infrequent dysphagia (every 2 months). All patients reported symptom severity of 1/10. Of Group B, all patients experienced pre-treatment dysphagia (daily to every few weeks). Pre-treatment symptom severity ranged 3-8/10 (average 5.8/10). Four patients started swallowed fluticasone. Five started PPIs. Five made diet changes. Post-treatment, one patient reported his dysphagia had completely resolved. Four reported infrequent dysphagia. One reported weekly dysphagia. Symptom severity ranged 1-7/10 (average 2.5/10). CONCLUSIONS: Immunotherapy may impart an added benefit to medications and diet changes in treatment of eosinophilic esophagitis in adult patients.
365
Innate Immune Responses Differ In Patients With Food Protein Induced Enterocolitis Syndrome (fpies) Who Respond Well To The Restrictive Diet And Those Who Do Not V. Rahimian, L. Geng, P. Kattouf, H. Jyonouchi; UMDNJ, Newark, NJ. RATIONALE: FPIES is a benign condition with an excellent response to the avoidance of the offending food, i.e., restrictive diet (RD). This study hypothesized that FPIES patients with poor responses to the RD (FPIESPR) have innate immune abnormalities compared to those with good responses to the RD (FPIES-GR). METHODS: This study include FPIES-PR (N518, 1.1 -5.1 yr), FPIES-GR (N518, 0.6-4.8 yr), and normal control (N516, 1.0-5.5 yr) children. In addition to detailed clinical features and routine food allergy (FA) workup, we examined responses to agonists of toll like receptors (TLRs) and representative luminal antigens (Ags) (soy, cow’s milk, and wheat proteins, and candida Ag) by measuring production of proinflammatory and counterregulatory cytokines by peripheral blood mononuclear cells (PBMCs) when their GI symptoms were under control following implementation of the RD. RESULTS: FPIES-PR children revealed more severe clinical features as evidenced by higher frequency of failure to thrive (FTT), requirement for the use of free amino acid (FAA) formulas, intolerance to probiotics, and severe anaphylaxis like reaction to rice than FPIES-GR children (all p<0.005). FPIES-PR PBMCs revealed lower production of counterregulatory cytokine (sTNFRII and IL-10) in the absence of stimulus and with TLR 5, 7/8, and 9 agonists (sTNFRII) and with TLR2/6, 5, and 9 agonists (IL-10) as compared to normal controls. FPIES-GR PBMCs only revealed lower IL-10 production with TLR2/6 agonist than controls. CONCLUSIONS: These findings indicate that decreased production of counter-regulatory cytokines in response to stimuli of innate immunity may be associated with apparent failure of developing oral tolerance in FPIES-PR children.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
SUNDAY
363
Histology Scoring System (HSS) is Superior to Peak Eosinophil Count (PEC) to Identify Treated vs Untreated Eosinophilic Esophagitis (EoE) Patients M. H. Collins1, L. J. Martin1, E. S. Alexander1,2, S. Pentiuk1, A. Ellison1, P. E. Putnam1, J. P. Franciosi1, J. P. Abonia1, M. E. Rothenberg1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2University of Cincinnati College of Medicine, Cincinnati, OH. _15 eosinophils per high power field in esophageal RATIONALE: PEC > biopsies is an EOE diagnostic criterion. We hypothesize greater discrimination among EoE biopsies occurs using a HSS including additional pathology (eosinophil abscesses/surface layering, epithelial hyperplasia and necrosis/ apoptosis, dilated intercellular spaces, lamina propria fibrosis). METHODS: Biopsy slides were scored retrospectively using an 8 point HSS to grade (measure severity) and stage (measure prevalence) histologic characteristics. Univariate data were analyzed using two-tailed Student _0.05. Wilcoxon 2-sample nonparametric tests were used to t-tests at p< _0.05. Logistic regression compare HSS parameters by treatment status at p< _0.05) with AICc were used to compare goodness of fit for models (p< models designed to predict treatment status. RESULTS: A total of 46 proximal and 42 distal esophageal biopsies from 41 patients were scored. Demographics were 81%male, 100%white, age 10.1664.53years (range3-18years) without differences between treated (diet and/or topical steroids) (35 endoscopies) vs untreated (11 endoscopies). Using nonparametric tests, PEC in distal (PECD) and proximal (PECP) biopsies, maximum PEC in either site (PECMax), and maximum stage (MSS) and grade (MGS) scores were associated with treatment status (p<0.01). Logistic regression models were significant for PECP and PECMax, and MSS and MGS, but not for PECD. Goodness of fit was superior for both MSS(42.79) and MGS(46.78), compared to PECP and PECMax(50.3,50.4) with MSS having the best fit. CONCLUSIONS: HSS is superior to eosinophil counts to identify EoE biopsies following therapy. HSS more completely evaluates mucosal healing than PEC, and likely forms a better basis for making therapeutic decisions.
Predicting Esophageal Biopsy Eosinophil Counts from Presenting Symptoms in Patients with Suspected Eosinophilic Esophagitis M. J. Greenhawt1, W. Rassbach2, M. Elkins2, J. K. Greenson1; 1The University of Michigan Medical School, Ann Arbor, MI, 2The University of Michigan Health System, Ann Arbor, MI. RATIONALE: Eosinophilic Esophagitis (EoE) is a clinicopathological condition hallmarked by esophageal eosinophilia >15 per high powered field(hpf) on biopsy. EoE symptomatology has considerable overlap with gastroesophageal reflux disease (GERD). No symptom patterns accurately distinguish the conditions without a biopsy. METHODS: Chart review of 504 consecutive pediatric and adult patients who underwent esophageal biopsy between 2008 and 2011. 19 symptoms were analyzed by logistic regression to determine their association with diagnostic cell counts indicative of EoE (> 15/hpf). RESULTS: 78.4% (388/495) had biopsies with diagnostic counts. Pediatric bivariate analysis indicated dysphagia to solids, duration of symptoms >6 months, and Caucasian race positively predicted; but weight loss/failure to thrive, vomiting, and abdominal pain negatively predicted diagnostic counts. On multivariate analysis, dysphagia to solids (OR 2.13, CI95%1.35-3.37, p>0.001) and weight loss (OR 0.406, CI95%0.21-0.784, p>0.007) predicted diagnostic counts. Adult bivariate analysis indicated regurgitation, atopy, and dysphagia to solids positively predicted; but early satiety, nocturnal awakening, weight loss, and reflux/heartburn negatively predicted diagnostic counts. On multivariate analysis, regurgitation (OR 2.29, CI95%1.1-4.74, p>0.025), dysphagia to solids (OR 1.82, CI95%1.13-2.93, p>0.013), early satiety (OR 0.359, CI95%0.14-0.898, p>0.029), weight loss (OR 0.463,CI95%0.0249-0.861, p>0.015) and chest pain (OR 0.55, CI95%0.310.975, p>0.041) predicted diagnostic counts. With multivariate adjustment for PPi use, dysphagia to solids and weight loss in adults remained significant. CONCLUSIONS: Dysphagia to solids positively predicted, and weight loss negatively predictive diagnostic counts in all ages, but after adjustment for PPi use only remained significant in adults. Further prospective study is needed for additional confirmation.
364
366
The Potential Benefit of Immunotherapy in the Treatment of Eosinophilic Esophagitis in Adult Patients S. Silverman, C. Bassett, E. Rothstein; New York University Langone Medical Center, New York, NY. RATIONALE: This study examined 2 groups of adult patients with eosinophilic esophagitis to assess immunotherapy’s possible added treatment benefit. METHODS: This was a retrospective chart review of 12 adult patients with eosinophilic esophagitis, diagnosed by esophageal biopsy. Group A included 6 patients (4 male, 2 female, ages 30-45), all receiving immunotherapy, medications, and diet changes. Group B included 6 patients (4 male, 2 female, ages 30-45), selected from 45 eosinophilic esophagitis patients to match age/gender distribution of Group A, on medications and diet changes alone. All patients were asked to rate symptom severity on a 1-10 scale (15nonexistent, 105most severe). RESULTS: Of Group A, all patients experienced pre-treatment dysphagia (daily to every few months). Pre-treatment symptom severity ranged 2-10/ 10 (average 6/10). All patients started swallowed fluticasone. Five started proton pump inhibitors (PPIs). Five made diet changes. All patients were on immunotherapy to treat seasonal allergies, for a period from 6 months to greater than 2 years. Post-treatment, 2 patients reported their dysphagia had completely resolved. Four reported infrequent dysphagia (every 2 months). All patients reported symptom severity of 1/10. Of Group B, all patients experienced pre-treatment dysphagia (daily to every few weeks). Pre-treatment symptom severity ranged 3-8/10 (average 5.8/10). Four patients started swallowed fluticasone. Five started PPIs. Five made diet changes. Post-treatment, one patient reported his dysphagia had completely resolved. Four reported infrequent dysphagia. One reported weekly dysphagia. Symptom severity ranged 1-7/10 (average 2.5/10). CONCLUSIONS: Immunotherapy may impart an added benefit to medications and diet changes in treatment of eosinophilic esophagitis in adult patients.
365
Innate Immune Responses Differ In Patients With Food Protein Induced Enterocolitis Syndrome (fpies) Who Respond Well To The Restrictive Diet And Those Who Do Not V. Rahimian, L. Geng, P. Kattouf, H. Jyonouchi; UMDNJ, Newark, NJ. RATIONALE: FPIES is a benign condition with an excellent response to the avoidance of the offending food, i.e., restrictive diet (RD). This study hypothesized that FPIES patients with poor responses to the RD (FPIESPR) have innate immune abnormalities compared to those with good responses to the RD (FPIES-GR). METHODS: This study include FPIES-PR (N518, 1.1 -5.1 yr), FPIES-GR (N518, 0.6-4.8 yr), and normal control (N516, 1.0-5.5 yr) children. In addition to detailed clinical features and routine food allergy (FA) workup, we examined responses to agonists of toll like receptors (TLRs) and representative luminal antigens (Ags) (soy, cow’s milk, and wheat proteins, and candida Ag) by measuring production of proinflammatory and counterregulatory cytokines by peripheral blood mononuclear cells (PBMCs) when their GI symptoms were under control following implementation of the RD. RESULTS: FPIES-PR children revealed more severe clinical features as evidenced by higher frequency of failure to thrive (FTT), requirement for the use of free amino acid (FAA) formulas, intolerance to probiotics, and severe anaphylaxis like reaction to rice than FPIES-GR children (all p<0.005). FPIES-PR PBMCs revealed lower production of counterregulatory cytokine (sTNFRII and IL-10) in the absence of stimulus and with TLR 5, 7/8, and 9 agonists (sTNFRII) and with TLR2/6, 5, and 9 agonists (IL-10) as compared to normal controls. FPIES-GR PBMCs only revealed lower IL-10 production with TLR2/6 agonist than controls. CONCLUSIONS: These findings indicate that decreased production of counter-regulatory cytokines in response to stimuli of innate immunity may be associated with apparent failure of developing oral tolerance in FPIES-PR children.