A concise review of opioid-induced esophageal dysfunction: is this a new clinical entity?

Opioids have become the most widely prescribed analgesics in Western countries. Opioid-induced bowel dysfunction is a widely known adverse effect, with constipation the most common manifestation. Most of the opioid-related effects occur in the stomach, small intestine, and colon and have been widely studied. However, the effects related to esophageal motility are less known. Recently published retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction, reflecting symptoms similar to motility disorders, such as achalasia and functional esophagogastric junction outflow obstruction. The most common manometric findings, as reported in the literature, for patients with opioid-induced dysphagia undergoing long-term therapy with these drugs are impaired lower esophageal sphincter relaxation, high amplitude/velocity, and simultaneous esophageal waves, higher integrated relaxation pressure, lower distal latency, and the esophageal contractility can be normal, hypercontractile, or premature. Based on these studies, a new clinical entity known as opioid-induced esophageal dysfunction has been postulated. For these patients, the diagnostic method of choice is high-resolution manometry, although other causes should be ruled out through endoscopy or Computed Tomography (CT). The best therapeutic option for these patients is withdrawal of the opioid; however, this is not always possible, and other options need to be investigated, such as pneumatic dilation and botulinum toxin injection, considering the risks versus the benefits.

Alpha-defensins (α-Defs) in Crohn's disease: decrease of ileal α-Def 5 via permanent methylation and increase in plasma α-Def 1-3 concentrations offering biomarker utility.

An impaired expression of α-defensins (α-Defs) in the ileal mucosa and, conversely, increased levels in plasma, have been reported in Crohn's disease (CD). However, the specificity and correlation of these findings with the degree of inflammation are unclear. We aimed to characterize the concentration and utility of ileal and plasma α-Defs in CD and to analyse a potential epigenetic mechanism of α-Def expression. Peripheral blood samples and ileal biopsies were obtained from patients at disease onset (aCD), from those who achieved remission (iCD) and from two control groups (healthy controls and non-CD-aetiology ileitis patients). Plasma α-Defs 1-3 and 4 were detected by enzyme-linked immunosorbent assay (ELISA); α-Def 5 by immunolocalization. Methylation analysis of the α-Def 5 gene was performed using the MassARRAY EpiTYPER system. Plasma α-Defs 1-3 concentrations were significantly higher in aCD with ileal involvement (L1, L3) versus iCD or the control groups. The α-Defs 1-3 concentrations were also similar to healthy controls in patients with non-CD ileitis. There was a significant positive correlation between plasma α-Defs 1-3 levels in aCD and the endoscopic index, as well as with C-reactive protein (CRP) levels. The immunopositivity scoring showed significantly reduced α-Def 5 expression in ileal inflamed (aCD) versus non-inflamed mucosa (iCD and healthy controls). The α-Def 5 gene showed a higher methylation status in CD patients than controls, regardless of the inflammation. Plasma α-Defs 1-3 concentrations correlate with the degree of inflammation and appear to be specific biomarkers of ileal-CD at diagnosis. Ileal α-Def 5 expression is down-regulated permanently by methylation.

Esophageal dysfunction and immunological changes induced by grass sublingual immunotherapy.

Sublingual immunotherapy frequently causes local oropharyngeal adverse events which are usually of mild severity, and tend to be self-limited and disappear within the first weeks of therapy. The mechanism of action involves changes in the specific humoral response to allergens, with increases in allergen-specific immunoglobulin G4 (IgG4) and blunting of the seasonal increase in allergen-specific IgE. We describe the case of a 25-year-old man diagnosed with grass pollen induced allergic rhinoconjunctivitis, who was treated with a lyophilisate of Phleum pratense by sublingual route. After 5 weeks of therapy he developed repeatedly intense symptoms of esophageal dysfunction immediately after the administration. Symptoms recurred every day, subsided in some hours without treatment and disappeared with the termination of therapy. The episode coincided with a marked elevation of total and specific IgE. The immunological changes gradually declined during the three years of follow up. The reported case suggests the need to evaluate the role of the immunological changes detected after the first weeks of sublingual therapy with Phleum pratense, in the induction of esophageal disorders.