Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease.

INTRODUCTION: Celiac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled. METHODS: We undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease. The 94-week study involved treatment with either 20 or 40 Necator americanus third-stage larvae (L3-20 or L3-40) or placebo, followed by escalating gluten consumption (50 mg/d for 12 weeks, 1 g intermittent twice weekly for 12 weeks, 2 g/d sustained for 6 weeks, liberal diet for 1 year). RESULTS: Successful study completion rates at week 42 (primary outcome) were similar in each group (placebo: 57%, L3-20: 37%, and L3-40: 44%; P = 0.61), however gluten-related adverse events were significantly reduced in hookworm-treated participants: Median (range) adverse events/participant were as follows: placebo, 4 (1-9); L3-20, 1 (0-9); and L3-40, 0 (0-3) (P = 0.019). Duodenal villous height:crypt depth deteriorated similarly compared with their enrolment values in each group (mean change [95% confidence interval]: placebo, -0.6 [-1.3 to 0.2]; L3-20, -0.5 [-0.8 to 0.2]; and L3-40, -1.1 [-1.8 to 0.4]; P = 0.12). A retrospective analysis revealed that 9 of the 40 L3-treated participants failed to establish hookworm infections. Although week 42 completion rates were similar in hookworm-positive vs hookworm-negative participants (48% vs 44%, P = 0.43), quality of life symptom scores were lower in hookworm-positive participants after intermittent gluten challenge (mean [95% confidence interval]: 38.9 [33.9-44] vs 45.9 [39.2-52.6]). DISCUSSION: Hookworm infection does not restore tolerance to sustained moderate consumption of gluten (2 g/d) but was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses.

Clinical and endoscopic features of eosinophilic esophagitis in adults.

BACKGROUND: Eosinophilic esophagitis in adults is regarded as unusual, being diagnosed mostly in young men presenting with dysphagia. Mucosal furrows are a sentinel endoscopic feature. This study examined the demographic and clinical profile of adults with eosinophilic esophagitis seen from 1981 to 2002. METHODS: All patients from an Australian provincial city (population 198,000) with otherwise unexplained eosinophilic inflammation of the squamous epithelium (>/=30 eosinophils per high-power field) were included in a retrospective review. RESULTS: A diagnosis of eosinophilic esophagitis was made in 31 patients (24 men, 7 women; mean age 34 years, range 14-77 years). The diagnosis was made in 19 (61%) of the 31 patients during the most recent 2 years (none between 1981 and 1994 vs. 12 between 1995-2000 vs. 19 between 2000-2001). Esophageal mucosal furrows were present in 30 (97%), a finding infrequently recognized before 2001. Dysphagia was documented in 26 (89%). Symptoms had been present for long periods before diagnosis (mean 54 months; range 0-180 months), and diagnosis was delayed in 7 (mean 81 months, range 20-144 months) because sentinel features were overlooked at endoscopy. Strictures, often evident only as a result of mucosal shearing during dilation, were present in 17 (57%). Esophageal dilation preformed in 17 (mean 3.4 dilations per patient, range 1-13) consistently relieved symptoms; tears were recorded in 13 (87%), but no serious complication resulted. CONCLUSIONS: Eosinophilic esophagitis in adults of all ages is more common than recognized. Mucosal furrows are easily overlooked at endoscopy although this finding is an important clue to diagnosis. Strictures, a frequent consequence, can be safely managed by dilation.