Dianne Jones

Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus.

Background and Goals Acute food bolus impaction is a common emergency in gastrointestinal practice. Management previously used the endoscope with an overtube to allow retrieval of the bolus per os. The push technique using air insufflation and gentle pressure on the bolus provides an alternative approach. Esophageal mucosal biopsy at the time of the initial endoscopy has not been a part of traditional practice. In view of the increasing recognition of eosinophilic esophagitis (EE) as a cause of dysphagia and food bolus obstruction in adults the etiology needs to be reassessed. Study Forty-three consecutive adults presenting with acute dysphagia secondary to food bolus obstruction of the esophagus were studied. The bolus was advanced into the stomach with the push technique or removed per os with a retrieval net. Protocol biopsies from the proximal and distal esophagus were obtained in 29 patients. Biopsies were contraindicated or not obtained in the remainder. Results Forty-one patients were successfully treated at endoscopy. Two subjects with a food bolus impacted at the crico-pharyngeal region required general anesthesia with endotracheal intubation for safe removal. Of 29 patients biopsied, 15 had peptic esophageal stricture as the cause. Fourteen patients (all males, mean age 32 y, range 19 to 62 y) had EE identified histologically. This represents 50% of those biopsied. Patients with EE had typical endoscopic features of linear furrows, mucosal rings, or narrow bore esophagus. Most had prior episodes of food bolus obstruction. Conclusions Food bolus obstruction can be safely managed by the push technique. EE is an important cause of food bolus obstruction that can be suspected on history and endoscopic appearance and confirmed on histology.

Effect of Hookworm Infection on Wheat Challenge in Celiac Disease – A Randomised Double-Blinded Placebo Controlled Trial

Background and Aims The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten. Methods In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3rd stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65)-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge. Results Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes. Conclusions Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology. Trial Registration ClinicalTrials.gov NCT00671138

Suppression of Inflammatory Immune Responses in Celiac Disease by Experimental Hookworm Infection

We present immunological data from two clinical trials where the effect of experimental human hookworm (Necator americanus) infection on the pathology of celiac disease was evaluated. We found that basal production of Interferon- (IFN-)γ and Interleukin- (IL-)17A from duodenal biopsy culture was suppressed in hookworm-infected participants compared to uninfected controls. Increased levels of CD4+CD25+Foxp3+ cells in the circulation and mucosa are associated with active celiac disease. We show that this accumulation also occurs during a short-term (1 week) oral gluten challenge, and that hookworm infection suppressed the increase of circulating CD4+CD25+Foxp3+ cells during this challenge period. When duodenal biopsies from hookworm-infected participants were restimulated with the immunodominant gliadin peptide QE65, robust production of IL-2, IFN-γ and IL-17A was detected, even prior to gluten challenge while participants were strictly adhering to a gluten-free diet. Intriguingly, IL-5 was produced only after hookworm infection in response to QE65. Thus we hypothesise that hookworm-induced TH2 and IL-10 cross-regulation of the TH1/TH17 inflammatory response may be responsible for the suppression of these responses during experimental hookworm infection.

Spur cell anaemia and hepatic iron stores in patients with alcoholic liver disease undergoing orthotopic liver transplantation

BACKGROUND Following orthotopic liver transplantation (OLT) histological examination of explant livers from patients with alcoholic liver disease (ALD) sometimes shows extensive iron deposits in a distribution suggestive of homozygous haemochromatosis. AIMS To use haemochromatosis gene (HFE) assays to distinguish between ALD with notable siderosis and hereditary haemochromatosis. To evaluate the possible influence of spur cell haemolytic anaemia on hepatic iron loading. PATIENTS Thirty seven patients with ALD were abstinent for at least six months prior to OLT. Twenty three patients had transferrin saturations greater than 55%, 16 also had increased serum ferritin (>350 micrograms/l). Eight of 37 (22%) explant livers had grade 3 or 4 hepatic iron deposition, predominantly in hepatocytes. Of these, four had a hepatic iron index greater than 1. 9 and most seemed to have spur cell haemolytic anaemia. METHODS Mutation analysis for C282Y and H63D mutations was performed on DNA extracts from peripheral blood or explant liver. Spur cell haemolytic anaemia was diagnosed when the haemoglobin was 105 g/l in the presence of notable acanthocytosis. RESULTS None of the eight patients with grade 3 or 4 hepatic iron had evidence of the C282Y mutation. Two of the eight were heterozygous for H63D. None of the remaining 28 patients tested showed homozygous HFE mutations. Spur cell anaemia was present in six of the eight patients with heavy iron deposition and only one of the remaining patients. CONCLUSIONS The HFE mutation was not present in these patients with advanced ALD and heavy iron loading. Spur cell haemolytic anaemia provides an alternative potential mechanism for the heavy iron loading.

Eosinophilic oesophagitis: epidemiology, pathogenesis and management.

Eosinophilic oesophagitis (EE) is a clinico-pathological entity recognized with increased frequency in children and adults. It is an atopic disease involving ingested and inhaled allergens. A pathological eosinophilic infiltrate is diagnosed by finding ≥15 eosinophils per high-powered field on oesophageal mucosal biopsies. This infiltrate may result in a narrowed oesophageal lumen. It does not involve the stomach or duodenum. Children commonly present with abdominal pain, vomiting and dysphagia. Presentation in adults is with dysphagia, heartburn, chest pain or impaction of a food bolus in the oesophagus. There is often a history of allergy (asthma, hay fever, eczema). A male predominance (70% in adults) is unexplained. Distinctive endoscopic features are linear furrows, mucosal rings and white papules, and the narrowed lumen may be appreciated. Although EE and gastro-oesophageal reflux disease are separate entities, there is a significant overlap of the conditions. Treatment options include nonpharmacological approaches including an elimination or elemental diet, and/ or medications, chiefly with corticosteroids. The topical administration of fluticasone propionate has been demonstrated to improve symptoms and mobilize the pathological infiltrate of eosinophils. There has been a variable effect with the leukotriene receptor antagonist montelukast and promising early results with mepolizumab, a monoclonal antibody against interleukin-5. The long-term efficacy of topical corticosteroids has not been well studied and most patients experience recurrent symptoms when treatment is completed. Currently, repeated short courses of topical corticosteroids are utilized. Acid suppression by a proton pump inhibitor may be considered in view of the overlap between EE and gastro-oesophageal reflux disease.

Australian Infection Control in Endoscopy Consensus Statements on Carbapenemase-producing Enterobacteriaceae: Australian Infection Control in Endoscopy Consensus Statements on Carbapenemase-producing Enterobacteriaceae

Outbreaks of carbapenemase‐producing Enterobacteriaceae clinical infections related to endoscopic transmission are well documented. The high morbidity and mortality associated with these infections emphasizes the need to reassess endoscopic reprocessing protocols. The Gastroenterological Society of Australia established a multi‐society committee to formulate evidence‐based consensus statements on the prevention and management of endoscopic transmission of carbapenemase‐producing Enterobacteriaceae. A literature search was undertaken utilizing the MEDLINE database. Further references were sourced from published paper bibliographies. Nine statements were formulated. Using the Delphi methodology, the statements were initially reviewed electronically by the committee members and subsequently at a face‐to‐face meeting in Melbourne, Australia. After further discussion, four additional sub‐statements were added resulting in a total of 13 statements. Each statement was assessed for level of evidence, recommendation grade and the voting on recommendation was recorded. For a statement to be accepted, five out of six committee members had to “accept completely” or “accept with some reservation.” All 13 statements achieved consensus agreement. Eleven statements achieved 100% “accepted completely.” Two statements were 83% “accepted completely” and 17% “accepted with some reservation.” Of particular significance, automated flexible endoscope reprocessors were mandated for high‐level disinfection, and the use of forced‐air drying cabinets was mandated for endoscope storage. These evidence‐based statements encourage preventative strategies with the aim of ensuring the highest possible standards in flexible endoscope reprocessing thereby optimizing patient safety. They must be considered in addition to the broader published guidelines on infection control in endoscopy.