A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

BACKGROUND: Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. METHODS: Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. RESULTS: 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. CONCLUSIONS: Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

Low incidence but poor prognosis of complicated coeliac disease: a retrospective multicentre study.

BACKGROUND: Coeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease. METHODS: Retrospective multicenter case-control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded. RESULTS: Between 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2-0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1-0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan-Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease. CONCLUSIONS: Complications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality.

Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity.

OBJECTIVES: Non-celiac wheat sensitivity (WS) is considered a new clinical entity. An increasing percentage of the general population avoids gluten ingestion. However, the real existence of this condition is debated and specific markers are lacking. Our aim was thus to demonstrate the existence of WS and define its clinical, serologic, and histological markers. METHODS: We reviewed the clinical charts of all subjects with an irritable bowel syndrome (IBS)-like presentation who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge in the years 2001-2011. One hundred celiac disease (CD) patients and fifty IBS patients served as controls. RESULTS: Two hundred and seventy-six patients with WS, as diagnosed by DBPC challenge, were included. Two groups showing distinct clinical characteristics were identified: WS alone (group 1) and WS associated with multiple food hypersensitivity (group 2). As a whole group, the WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls. There was also a higher frequency of positive serum assays for IgG/IgA anti-gliadin and cytometric basophil activation in "in vitro" assay. The main histology characteristic of WS patients was eosinophil infiltration of the duodenal and colon mucosa. Patients with WS alone were characterized by clinical features very similar to those found in CD patients. Patients with multiple food sensitivity were characterized by clinical features similar to those found in allergic patients. CONCLUSIONS: Our data confirm the existence of non-celiac WS as a distinct clinical condition. We also suggest the existence of two distinct populations of subjects with WS: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.

Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis.

BACKGROUND: Celiac disease (CD) diagnosis is becoming more difficult as patients with no intestinal histology lesions may also be suffering from CD. AIM: To evaluate the diagnostic accuracy of antiendomysium (EmA) assay in the culture medium of intestinal biopsies for CD diagnosis. PATIENTS AND METHODS: The clinical charts of 418 patients with CD and 705 non-CD controls who had all undergone EmA assay in the culture medium were reviewed. RESULTS: EmA assay in the culture medium had a higher sensitivity (98 vs. 80%) and specificity (99 vs. 95%) than serum EmA/antibodies to tissue transglutaminase (anti-tTG) assay. All patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG (32 adults and 39 children) carried the human leukocyte antigen alleles associated to CD. Furthermore, during the follow-up, four patients with negative-serum EmA/anti-tTG, normal villi architecture, and positive-EmAs in the culture medium, developed villous atrophy and underwent gluten-free diet with consequent resolution of the symptoms and complete intestinal histology recovery. CONCLUSION: EmA assay in the culture medium should be included in the diagnostic criteria for CD diagnosis in 'seronegative' patients.

Fecal assays detect hypersensitivity to cow's milk protein and gluten in adults with irritable bowel syndrome.

BACKGROUND & AIMS: Some patients with irritable bowel syndrome (IBS)-like symptoms suffer from food hypersensitivity (FH); their symptoms improve when they are placed on elimination diets. No assays identify patients with FH with satisfactory levels of sensitivity. We determined the frequency of FH among patients with symptoms of IBS and the ability of fecal assays for tryptase, eosinophil cationic protein (ECP), or calprotectin to diagnose FH. METHODS: The study included 160 patients with IBS, 40 patients with other gastrointestinal diseases, and 50 healthy individuals (controls). At the start of the study, patients completed a symptom severity questionnaire, fecal samples were assayed, and levels of specific immunoglobulin E were measured. Patients were observed for 4 weeks, placed on an elimination diet (without cow's milk and derivatives, wheat, egg, tomato, and chocolate) for 4 weeks, and kept a diet diary. Those who reported improvements after the elimination diet period were then diagnosed with FH, based on the results of a double-blind, placebo-controlled, oral food challenge (with cow's milk proteins and then with wheat proteins). RESULTS: Forty of the patients with IBS (25%) were found to have FH. Levels of fecal ECP and tryptase were significantly higher among patients with IBS and FH than those without FH. The ECP assay was the most accurate assay for diagnosis of FH, showing 65% sensitivity and 91% specificity. CONCLUSIONS: Twenty-five percent of patients with IBS have FH. These patients had increased levels of fecal ECP and tryptase, indicating that they might cause inflammation in patients with IBS. Fecal assays for ECP could be used to identify FH in patients with IBS.

Searching for wheat plants with low toxicity in celiac disease: Between direct toxicity and immunologic activation.

BACKGROUND: Natural or induced variations in the noxiousness of gluten proteins for celiac disease (CD) patients are currently being investigated for their potential in breeding wheat crops with reduced toxicity. AIMS: We evaluated the bread wheat line C173 for its effects on the in vitro-grown duodenal mucosa of CD patients. METHODS: In vitro-grown duodenal mucosa biopsies of 19 CD patients on a gluten-free diet were exposed to peptic/tryptic-digested prolamins from bread wheat line C173 lacking gliadin-glutenin subunits, analyzed for morphology, cytokine and anti-tTG antibody production, and compared with mucosa biopsies exposed to prolamins from wild-type cv. San Pastore. RESULTS: Duodenal mucosa biopsies exposed to prolamins from C173 and San Pastore released higher amounts of IFN-γ, IL-2, IL-10 and anti-tTG antibodies in the culture medium than untreated controls. The line C173 differed from cv. San Pastore as it did not produce negative effects on enterocyte height, suggesting that manipulating prolamin composition can affect innate immune responses of CD mucosa to wheat gluten. CONCLUSIONS: Our data demonstrated that this gliadin-deficient wheat has a lower direct toxicity but activates an immunologic reaction of the duodenal mucosa like that of the common wheat species.

A cytologic assay for diagnosis of food hypersensitivity in patients with irritable bowel syndrome.

BACKGROUND & AIMS: A percentage of patients with symptoms of irritable bowel syndrome (IBS) suffer from food hypersensitivity (FH) and improve on a food-elimination diet. No assays have satisfactory levels of sensitivity for identifying patients with FH. We evaluated the efficacy of an in vitro basophil activation assay in the diagnosis of FH in IBS-like patients. METHODS: Blood samples were collected from 120 consecutive patients diagnosed with IBS according to Rome II criteria. We analyzed in vitro activation of basophils by food allergens (based on levels of CD63 expression), as well as total and food-specific immunoglobulin (Ig)E levels in serum. Effects of elimination diets and double-blind food challenges were used as standards for FH diagnosis. RESULTS: Twenty-four of the patients (20%) had FH (cow's milk and/or wheat hypersensitivity); their symptom scores improved significantly when they were placed on an elimination diet. Patients with FH differed from other IBS patients in that they had a longer duration of clinical history, a history of FH as children, and an increased frequency of self-reported FH; they also had hypersensitivities to other antigens (eg, egg or soy). The basophil activation assay diagnosed FH with 86% sensitivity, 88% specificity, and 87% accuracy; this level of sensitivity was significantly higher than that of serum total IgE or food-specific IgE assays. CONCLUSIONS: A cytometric assay that quantifies basophils after stimulation with food antigens based on cell-surface expression of CD63 had high levels of sensitivity, specificity, and accuracy in diagnosing FH. This assay might be used to diagnose FH in patients with IBS-like symptoms.

Clinical symptoms in celiac patients on a gluten-free diet.

OBJECTIVE: Persistent villous atrophy in patients with celiac disease (CD) on a gluten-free diet (GFD) is reported with increasing frequency. The aim of this study was to evaluate a possible association between persistent damage of the villi and "atypical" gastrointestinal symptoms in CD patients on a GFD. MATERIAL AND METHODS: Sixty-nine CD patients on a GFD were divided into two groups: Group A included 42 patients (6 M, 36 F, age range 17-62 years) undergoing esophagogastroduodenoscopies (EGDs) due to the presence of symptoms; Group B included 27 control patients (6 M, 21 F, age range 24-71 years) who were asymptomatic at the time of the study. Both groups underwent EGDs and a duodenal histologic study. RESULTS: Persistent endoscopic lesions were more frequent in Group A (30/42) than in Group B (12/27; p=0.01). Villous atrophy was significantly more frequent in Group A than in Group B: 85% versus 33% (p<0.0001; odds ratio (OR)=12; 95% CI 3.7-38.9). Gastrointestinal symptoms in the Group A patients were different from those present at CD diagnosis: anemia/diarrhea/weight loss in 6 cases; gastroesophageal reflux disease (GERD)-like symptoms in 12 cases; abdominal pain/constipation in 24 cases. In Group A there was no difference in gender distribution, age and duration of GFD between subjects with normal villi and those with persistent partial villous atrophy. Patients with persistent symptoms showed a higher intraepithelial eosinophil count (p=0.005) than the asymptomatic patients (p=0.01). CONCLUSIONS: Persistent intestinal villous atrophy in CD patients on a GFD is associated with gastrointestinal symptoms considered "atypical" for CD and not present at CD diagnosis.

[Anti-TNF (infliximab) treatment in Crohn disease: safety profile]. / Terapia biologica con infliximab (anti-TNF) nella malattia di Crohn: analisi delle complicanze.

Anti-tumor necrosis factor (anti-TNF) therapy is an important therapeutic addition in the treatment of active Crohn's disease. Although controlled trials have confirmed the efficacy of anti-TNF (infliximab) treatment, serious toxicities related to the therapies have emerged. The purpose of this article was to review the safety profile of infliximab, and in particular analyse the infectious complications, the autoimmune disorders and the theoretical risk of cancer and lymphoma.