Nicholas J. Shaheen, MD. MPH Center for Esophageal Diseases and Swallowing University of North Carolina SOM

Transcription

1 Eosinophilic Esophagitis: Are We There Yet? Nicholas J. Shaheen, MD. MPH Center for Esophageal Diseases and Swallowing University of North Carolina SOM Learning Objectives Understand current definition of EoE Know the DDx and appropriate ways of making the diagnosis Be familiar with first- and second-line medical therapies for the condition State the complication rate associated with endscopic therapy of EoE 1

2 Food Backing Up 22 yo M w/ 6 mo h/o solid food dysphagia Food sticking in upper chest with most meals Symptoms progressed decr d po w/ 20# wt loss Associated history of seasonal allergies No known food allergies Goes To Upper Endoscopy Does this pt have EoE? 2

3 Histopathologic findings Max 45 eos/hpf Courtesy of Dr. John T. Woosley, UNC Biopsy yield by diagnostic cut-point Gonsalves et al, GIE, 2006; similar data in Shah et al, AJG,

4 ACG EoE clinical guidelines EoE diagnostic criteria: Symptoms related to esophageal dysfunction Eosinophil-predominant inflammation on esophageal biopsy, characteristically with 15 eos/hpf Mucosal eosinophilia is isolated to the esophagus and persists after a PPI trial Secondary causes of esophageal eosinophilia excluded Am J Gastroenterol, 2013 EoE DDx of esophageal eosinophilia Eosinophilic gastroenteritis GERD Crohn s disease Connective tissue diseases Hypereosinophilic syndrome Infections Drug hypersensitivity response Furuta et al, Gastro,

5 DDx of esophageal eosinophilia EoE Eosinophilic gastroenteritis GERD Crohn s disease Connective tissue diseases Hypereosinophilic syndrome Infections Drug hypersensitivity response - Common - Frequent EGDs - Clinical overlap - Diagnostic overlap Furuta et al, Gastro, 2007 GERD and EoE GERD referral center, retrospective data ( ) 40 of 3,648 (1.1%) of adult patients were found to have > 20 eosinophils per high-powered field (eos/hpf) Rodrigo et al, Am J Gastro,

6 GERD and EoE Underlying condition Eosinophil counts (range of max # per hpf) EoE (n = 6) EoE + GERD (n = 2) GERD (n = 28) Other (achalasia; diverticula; n = 4) Rodrigo et al, Am J Gastro, 2008 PPI-REE Retrospective review of index EGDs and biopsies for patients with suspected EoE ( 15 eos/hpf): n = 36 Rx: BID PPI x 3 mos Histologic response n = 14 Dx: PPI-REE (not EoE) No histologic response n = 22 Dx: EoE Sayeh, J Pediatr Gastro Nutr, 2009; similar data: Dranove, J Peds,

7 PPI-REE at UNC 173 w/ dysphagia 65 w/ eos 15/hpf (38%) 24 PPI-REE (14%) 40 EoE (23%) 1 EoG w/ EoE (0.6%) 9 GERD type (5%) 12 EoE type (7%) 3 unknown type (2%) Clinical characteristics predictors? PPI-REE (n = 24) EoE (n = 40) p Age (mean ± SD) 48 ± ± 11 < Male (%) White (%) Symptoms (%) Dysphagia Heartburn Abdominal pain Nausea/vomiting Blood testing IgE level (mean ± SD) 230 ± ± Histology Max eos/hpf (mean ± SD) 50 ± ±

8 Clinical characteristics predictors? PPI-REE (n = 24) EoE (n = 40) p Age (mean ± SD) 48 ± ± 11 < Male (%) White (%) Symptoms (%) Dysphagia Heartburn Abdominal pain Nausea/vomiting Blood testing IgE level (mean ± SD) 230 ± ± Histology Max eos/hpf (mean ± SD) 50 ± ± Clinical characteristics predictors? PPI-REE (n = 24) EoE (n = 40) p Age (mean ± SD) 48 ± ± 11 < Male (%) White (%) Symptoms (%) Dysphagia Heartburn Abdominal pain Nausea/vomiting Blood testing IgE level (mean ± SD) 230 ± ± Histology Max eos/hpf (mean ± SD) 50 ± ±

9 Clinical characteristics predictors? PPI-REE (n = 24) EoE (n = 40) p Age (mean ± SD) 48 ± ± 11 < Male (%) White (%) Symptoms (%) Dysphagia Heartburn Abdominal pain Nausea/vomiting Blood testing IgE level (mean ± SD) 230 ± ± Histology Max eos/hpf (mean ± SD) 50 ± ± Clinical characteristics predictors? PPI-REE (n = 24) EoE (n = 40) p Age (mean ± SD) 48 ± ± 11 < Male (%) White (%) Symptoms (%) Dysphagia Heartburn Abdominal pain Nausea/vomiting Blood testing IgE level (mean ± SD) 230 ± ± Histology Max eos/hpf (mean ± SD) 50 ± ±

10 Clinical characteristics predictors? PPI-REE (n = 24) EoE (n = 40) p Age (mean ± SD) 48 ± ± 11 < Male (%) White (%) Symptoms (%) Dysphagia Heartburn Abdominal pain Nausea/vomiting Blood testing IgE level (mean ± SD) 230 ± ± Histology Max eos/hpf (mean ± SD) 50 ± ± Clinical characteristics predictors? PPI-REE (n = 24) EoE (n = 40) p Age (mean ± SD) 48 ± ± 11 < Male (%) White (%) Symptoms (%) Dysphagia Heartburn Abdominal pain Nausea/vomiting Blood testing IgE level (mean ± SD) 230 ± ± Histology Max eos/hpf (mean ± SD) 50 ± ±

11 Endoscopic findings not universal Kim et al, CGH, 2012 Endoscopic findings not universal Kim et al, CGH,

12 Endoscopic findings not universal Kim et al, CGH, 2012 EoE treatment options Pharmacologic therapy Acid suppression Corticosteroids (systemic; topical) Leukotriene antagonists (montelukast) Mast cell stabilizers (cromolyn) Immunomodulators (6-MP; azathioprine) Biologics (anti-il-5; anti-ige; anti-tnf) Dietary therapy Endoscopic therapy (dilation) No FDA-approved medications for EoE! 12

13 Topical steroids eosinophil counts 71% histologic response Year Design RCT RCT (open) RCT RCT RCT RCT Subjects 36 children 80 children 36 adults 24 children 34 adults 81 children Med FP 880/d FP /d* Bud 2mg/d** Bud 1-2mg/d*** FP 1560/d Bud mg/d*** Rx time 3 mos 12 wks 15 days 3 mos 6 wks 12 wks *Compared to prednisone; **Swallowed nebulized budesonide; ***oral viscous budesonide Topical steroids symptoms Year Design RCT RCT (open) RCT RCT RCT RCT Subjects 36 children 80 children 36 adults 24 children 34 adults 81 children Med FP 880/d FP /d* Bud 2mg/d** Bud 1-2mg/d*** FP 1560/d Bud mg/d*** Rx time 3 mos 12 wks 15 days 3 mos 6 wks 12 wks *Compared to prednisone; **Swallowed nebulized budesonide; ***oral viscous budesonide 13

14 Which steroid formulation? Open label RCT N=25 (22 with complete follow-up data) 1 mg bid dosing for both formulations x 8 wks Gastro, 2012 Histology and symptom response p = 0.62 p = 0.79 p = 0.02 p = 0.03 Dellon et al, Gastroenterology,

15 Histology and symptom response p = 0.62 p = 0.79 p = p = p = 0.30 p = 0.03 MDQ dysphagia score p = 0.31 p = Nebulized Viscous Baseline Dellon et al, Gastroenterology, 2012 Post-treatment Improvement with steroid therapy Before topical steroids After topical steroids Patient 1 Patient 2 Patient 3 Dellon et al, Gastro

16 Esophgeal emptying OVB static images NEB static images Patient 1: Patient 2: Patient 3: Patient 4: Dellon et al, Gastro, 2012 Dietary therapy in EoE The best therapy (particularly in children)? Rationale: food allergens may contribute to the pathogenesis of EoE Downsides: reliability of detecting food allergy difficulty with dietary compliance most research to date is in children 16

17 Prospective Study of SFED in Adults 50 adults with EoE 6 weeks SFED (milk, soy, egg, wheat, peanuts, shellfish/fish Reintroduction phase: one food group every 2 weeks order of food based on allergy testing or pt preference Gonsalves N et al, Gastro Dilation and complications Complications (n, %) Author Year n* Perfs Boerhaave s Tears/ Chest pain (spontaneous) rents (hospitalized) Vasilopoulos (0) -- 5 (100) 2 (40) Croese (0) (76) -- Straumann (0) -- 5 (100) -- Kaplan * 1 (13) -- 5 (63) -- Potter (0) (77) 2 (15) Cohen (8) 1(3) 7 (19) -- (Multiple other case reports of esophageal perforation (both spontaneous and as a result of endoscopic intervention) in patients with EoE: Ligouri, World J Gastro, 2008; Lucendo, Endoscopy, 2007; Eisenbach, Endoscopy, 2006; Prasad, Dis Esoph, 2005; Riou, Ann Thorac Surg, 1996) *number of dilations reported, with the exception of Kaplan where it is the number of EGDs 17

18 Less risk in the modern era? Complications (n, %) Author Year n* Perfs Boerhaave s Tears/ Chest pain (spontaneous) rents (hospitalized) Gonsalves (0) (0.7) Schoepfer (0) Straumann * 0 (0) 1 (0.8) Dellon (0) -- 2 (3) 1 (1) Shepherd (0) Schoepfer e * 0(0) ** Bohm (0) Jung (1) (9) -- * number of dilations reported, except Straumann (EGDs), Shoepfer (patients), and Bohm (patients) ** 74% of patients (n=42) had some complaint of post-procedural chest pain; in 17% it was severe; however, there was a high degree of patient acceptance of this procedure Does EoE progress? Inflammatory Adult Dysphagia Food impaction Child Failure to thrive Vomiting Fibrotic Age 18

19 Delay in diagnosis and strictures OR = 1.08/yr (~ for each decade) Schoepfer et al, Gastro, 2013 EoE as a progressive disease Retrospective study of the UNC EoE Database n = 374 EoE cases; 3 phenotypes: Inflammatory (n = 134; 36%) Mixed (n = 163, 43%) Fibrostenotic (n = 77; 21%) Age (years) <0.001 Dysphagia (%) <0.001 Food impaction (%) <0.001 Heartburn (%) Vomiting (%) <0.001 Failure to thrive (%) <0.001 Allergic diseases (%) Food allergy (%) Eosinophil count (eos/hpf) p Dellon et al, GIE, in press

20 EoE as a progressive disease 1 ng Predicted d probability of developi fibrostenosis Predicted probability Upper 95% CI Lower 95% CI OR = 2.1 ( ) per 10 year increase for developing a fibrostenotic EoE phenotype Age (years) Dellon et al, GIE, in press 2013 Summary algorithm Clinical suspicion - Dysphagia - Food impaction - Refractory GERD - Peds can be atypical Endoscopic findings biopsy! - Rings/strictures - Furrows - Exudates/plaques - Tears - Normal 15 eos/hpf* (exclude other causes) 20

21 Summary algorithm Suspected EoE ( 15 eos/hpf) PPI trial (2 mos) 15 eos/hpf; ongoing symptoms < 15 eos/hpf; sx resolved GERD PPI-REE Monitor while continuing PPI EoE Topical steroids or dietary therapy as first line rx Inadequate response Adequate response Switch from steroid to dietary therapy, or vice versa Dilation Exclude infection Consider prednisone or other agents Monitor; consider maintenance therapy 21