Eosinophilic esophagitis and duodenal food challenge - evaluation through endoscopic confocal laser endomicroscopy.

BACKGROUND: Endoscopic confocal laser endomicroscopy (eCLE) is an established technique that allows clinical evaluation of mucosal integrity by fluorescein leaking through the mucosa upon duodenal food challenge (DFC). Analysis of eCLE with DFC in eosinophilic esophagitis (EoE) would be interesting to evaluate epithelial barrier dysfunction also in other regions of the gastrointestinal tract and to characterize potential individual food allergens that trigger the esophageal inflammation. METHODS: In an observational and proof of concept study we evaluated 9 patients with histologically proven EoE by eCLE and DFC. Severity of symptoms were graduated according to the validated symptom-based EoE activity index. The endoscopic appearance of the esophagus was described according to the Endoscopic Reference Score System (ERERS). Spontaneous and food induced transfer of fluorescein into duodenal lumen were detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC. Food allergens were yeast, egg, soy, milk, and wheat, respectively. Local application of sodium chloride solution 10 % to the duodenal mucosa before DFC served as a control. Patients responding to DFC received a dietary exclusion therapy according to the results of DFC. RESULTS: We investigated 9 patients with EoE (8 men, 49.7±13.8, 36-76 years). Symptom-based EoE activity index was 79±27.4, 33-100. In all patients EoE was confirmed by histology with number of esophageal mucosal eosinophilic granulocytes > 15/HPF, (91.4±77.4, 42-263). Mean ERERS score was 4.5±1.3, 3-7. None of the patients was aware of any food intolerance. eCLE revealed one patient with spontaneous transfer of i. v. fluorescein into duodenal lumen before DFC ("leaky gut"). 40 DFC were performed in the remaining 8 patients of whom 5 patients (61 %) responded to DFC. Rank order of fluorescein leakage upon DFC was wheat and milk in 37.5 % each, soy in 25 %, and egg in 12.5 %. The patients were treated by PPI (n=9), esophageal bouginage (n=5) and/or local corticoid therapy (n=3). The 5 patients responding to DFC received an additional food exclusion dietary advice focussed on the results of DFC. All patients reported a reduction of their symptoms. EoE activity indexes of patients with positive DFC were 73.7+28.6, 33-100 before and 22.7+37.9, 0-79 four weeks after food exclusion. CONCLUSION: The findings of our proof of concept study suggest that eCLE with DFC may be an interesting tool to further evaluate patients with EoE. This technique has the potential to identify patients who may benefit from an additional individual dietary therapy.

Autoimmune encephalitis and gastrointestinal dysmotility: achalasia, gastroparesis, and slow transit constipation.

BACKGROUND: Neurological autoimmune disorders (NAD) are caused by autoimmune inflammation triggered by specific antibody subtypes. NAD may disturb the gut-brain axis at several levels including brain, spinal cord, peripheral, or enteric nervous system. CASE REPORT: We present a case with antinuclear neuronal Hu (ANNA-1)- and antiglial nuclear (SOX-1) autoimmune antibody-positive limbic encephalitis and significant gastrointestinal dysmotility consisting of achalasia type II, gastroparesis, altered small intestinal interdigestive motility, and severe slow transit constipation. The autoantibodies of the patient's serum labeled enteric neurons and interstitial cells of Cajal but no other cells in the gut wall. Achalasia was treated successfully by pneumatic cardia dilation and gastrointestinal dysmotility successfully with prucalopride. CONCLUSION: NAD may disturb gastrointestinal motility by altering various levels of the gut-brain axis.

Eosinophilic esophagitis and achalasia - just a coincidence?

BACKGROUND: Eosinophilic esophagitis (EoE) is detected frequently in dysphagia and noncardiac chest pain. Management of patients with EoE may be complicated because EoE is associated frequently with esophageal motility disorders. We present the rare case of esophageal achalasia (EA) associated with eosinophilic infiltration and a literature review. MATERIAL AND METHODS: A patient with dysphagia and eosinophilic infiltration referred to our clinic underwent standardized diagnostic work-up including symptom questionnaire, esophagogastroduodenoscopy (EGD) with esophageal biopsies, barium swallow, high-resolution esophageal manometry, and combined intraluminal 24-hour pH-impedance testing (pH/MII). RESULTS: The patient had an Eckardt score of 8. EGD and mucosal biopsies showed typical EoE with > 15 eosinophil leucocytes per high-power field. Barium swallow revealed typical sign of achalasia. HREM indicated EA type 2 according to the Chicago classification. PH/MII was normal. Oral and systemic corticoid therapy were without effect. After successful treatment by pneumatic dilation of the cardia, symptoms relieved and eosinophilic infiltration returned to normal. CONCLUSION: The results suggest that the patient had primary EA associated with eosinophilic infiltration and that the combined occurrence of these rare diseases is not just a coincidence.

Peroral endoscopic myotomy (POEM) is effective in treatment of noncardiac chest pain caused by hypercontractile esophageal motility disorders: results of the POEM-HYPE-Study.

BACKGROUND: Noncardiac chest pain (NCCP) is recurrent angina pectoris-like pain without evidence of coronary heart disease in conventional diagnostic evaluation. In gastroenterology, managing of patients with NCCP is ambiguous to detect gastroesophageal reflux and hypercontractile esophageal motility disorders. Recently, peroral endoscopic myotomy (POEM) was established as treatment option in achalasia. However, limited data exist on the effectivity of POEM in NCCP with hypercontractile esophageal motility disorders. MATERIAL AND METHODS: In this prospective study (POEM-HYPE), we evaluated 14 patients with NCCP and hypercontractile esophageal motility disorders (type III achalasia, n = 7; hypercontractile esophagus, n = 6; distal esophageal spasm, n = 1). All patients underwent standardized diagnostic work-up including esophagogastroduodenoscopy with esophageal biopsies, high-resolution esophageal manometry, and combined intraluminal impedance and pH testing before and 3 weeks after POEM. A standardized symptom questionnaire was disposed before POEM, 3 weeks after, and every 6 months after the POEM. RESULTS: After POEM, 12 patients showed significant symptom relief (pre-Eckardt score: 7.78 ±â€Š1.47, 3 weeks post: 1.64 ± 1.44, 6 months: 2.0 ±â€Š1.84 and 1.86 ±â€Š1.89 after 15.0 ±â€Š10.0 months post-intervention). High-resolution manometry showed significant reduction in integrated relaxation pressure (pre-POEM: 24.74 ±â€Š18.9 mm Hg, post-POEM: 13.8 ±â€Š16.5 mm Hg) and distal contractile integral (pre-POEM: 2880 ±â€Š3700 mmHg*s*cm, post-POEM: 1109 ±â€Š1042 mmHg*s*cm). One lesion of the submucosal tunnel occurred as a moderate adverse event and was handled endoscopically. The long-term clinical success rate was 85.7 %. No severe gastroesophageal reflux occurred after interventions. Two patients required secondary therapy with injection of botulinum toxin in the tubular esophagus and balloon dilation. CONCLUSION: The results suggest that POEM is an effective and safe therapeutic option for patients with NCCP and hypercontractile esophageal motility disorders.