Short article: Mortality and differential diagnoses of villous atrophy without coeliac antibodies.

OBJECTIVE: Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. PATIENTS AND METHODS: Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed. RESULTS: Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients. CONCLUSION: Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.

A second duodenal biopsy is necessary in the follow-up of adult coeliac patients.

INTRODUCTION: Coeliac disease is a chronic enteropathy requiring a close follow-up. However, the best way to follow up coeliac patients has not yet been established. In the last 14 years, we have been offering patients a thorough series of periodical examinations including a histological re-evaluation at 12-18 months. PATIENTS AND METHODS: The notes of all coeliac patients attending our clinic between September 1999 and March 2013 were examined. RESULTS: Data from 317 adult patients were collected. Duodenal biopsy showed a lack of satisfactory histological response in 25/317 patients; endomysial antibodies were still positive in 76, and diet adherence and clinical response were unsatisfactory in 58 and 97, respectively. Correlations of serological data, clinical response, and diet adherence with histological findings were evaluated. Although the P values showed statistically significant differences, sensitivity and specificity were disappointing: 64% and 80% for serological response, 48% and 71% for clinical response, 56% and 85% for diet adherence. CONCLUSIONS: After 12-18 months on a gluten-free diet, 8% of the patients do not present a satisfactory histological response; only some of them could have been identified with a serological and/or clinical re-evaluation. Therefore, a duodenal biopsy seems to be the only tool that could identify patients with unsatisfactory histological response.

Dental enamel defects in adult coeliac disease: prevalence and correlation with symptoms and age at diagnosis.

BACKGROUND: Coeliac disease is a condition characterized by a wide spectrum of clinical manifestations. Any organ can be affected and, among others, dental enamel defects have been described. Our aims were to study the prevalence of dental enamel defects in adults with coeliac disease and to investigate a correlation between the grade of teeth lesion and clinical parameters present at the time of diagnosis of coeliac disease. METHODS: A dental examination was performed in 54 coeliac disease patients (41 F, mean age 37 ± 13 years, mean age at diagnosis 31 ± 14 years). Symptoms leading to diagnosis were diarrhoea/weight loss (32 pts.), anaemia (19 pts.), familiarity (3 pts.); none of the patients was diagnosed because of enamel defects. At the time of evaluation, they were all on a gluten-free diet. Enamel defects were classified from grade 0 to 4 according to its severity. RESULTS: Enamel defects were observed in 46/54 patients (85.2%): grade 1 defects were seen in 18 patients (33.3%) grade 2 in 16 (29.6%), grade 3 in 8 (14.8%), and grade 4 in 4 (7.4%). We also observed that grades 3 and 4 were more frequent in patients diagnosed with classical rather than non-classical coeliac disease (10/32 vs. 2/20). However, this was not statistically significant. CONCLUSION: This study confirms that enamel defects are common in adult coeliac disease. Observation of enamel defects is an opportunity to diagnose coeliac disease.

Prevalence and natural history of potential celiac disease in adult patients.

OBJECTIVE: Potential celiac disease (PCD) is a form of CD characterized by positive endomysial/tissue transglutaminase antibodies and a preserved duodenal mucosa despite a gluten-containing diet (GCD); it can evolve into flat, active CD. This evolution is, however, not certain. Our aim was to retrospectively study the prevalence and the natural history of adult patients with PCD. METHODS: The clinical notes of all 47 patients with PCD attending our clinic between September 1999 and October 2011 were retrospectively reevaluated. To study their clinical features, patients with active CD, randomly selected and matched for sex and date of birth, served as controls. Symptoms, associated diseases, familiarity, and laboratory data at diagnosis were compared. RESULTS: Prevalence of PCD among all celiac patients directly diagnosed in our center was 42/187, (1/4.4, 18.3%, 95% confidence interval (CI) 13.3-23.4%). Age at diagnosis, laboratory data, prevalence of symptoms, associated diseases, and familiarity for CD did not differ between patients with PCD and those with active CD. Some patients with PCD maintained a normal duodenal mucosa for many years and their symptoms spontaneously improved despite maintaining a GCD. CONCLUSIONS: PCD is not a rare form of CD. Having found no difference at all in age at diagnosis and clinical features between PCD and active CD could suggest that PCD is not a prodrome of CD but is a separate entity that can only subsequently evolve into active CD.

Quality of life in coeliac patients: Italian validation of a coeliac questionnaire.

BACKGROUND: Coeliac disease (CD) is a chronic condition requiring a gluten-free diet, which is a very demanding diet to maintain on a life-long basis. For this reason it is a condition that can have serious repercussions on the quality of life (QOL). Therefore the need to elaborate a questionnaire on QOL specifically for patients with CD (CDQ): its original language is German, and the translation/validation process represents a considerable challenge involving not only a translation into Italian but also an adaptation to the country's specific cultural differences. METHODS: The questionnaire has been translated according to a "German → Italian → Italian → German" algorithm with reconciliation of the differences. Scores for CDQ are computed overall and over four areas of four items each: emotion, gastrointestinal symptoms, gastrointestinal worries, social problems. RESULTS: CDQ was administered to 171 coeliacs (F 132, mean age 38 yrs ± 14). Completeness was optimal. Item internal consistency was satisfied for 100% and 97% of patients for the specific and generic part, respectively. Cronbach's α coefficient was 0.7 for all scales. The general CDQ was higher in patients reporting subjective well-being (discriminant validity). CONCLUSIONS: The Italian translation of CDQ sounds natural, is easy to understand and reduces possible cultural biases to a minimum. A field test gave results comparable to the original validation, supporting the use of CDQ in cross-national surveys.

Previous immunosuppressive therapy is a risk factor for immune reconstitution inflammatory syndrome in Whipple's disease.

INTRODUCTION: Whipple's disease is a rare chronic infection caused by Tropheryma whipplei. Although most patients respond to antibiotics, in some of them the start of the treatment is followed by recurrence of inflammation. Since polymerase chain reaction is negative for Tropheryma whipplei, this reinflammation cannot be a relapse of Whipple's disease itself. Very recently, it has been recognised as a complication of Whipple's disease and defined immune reconstitution inflammatory syndrome (IRIS). Our aim is to study the prevalence and the clinical features of IRIS in Italian patients with Whipple's disease. METHODS: Evidence of IRIS was retrospectively revaluated in the clinical notes of 22 patients with Whipple's disease. Patients with no evidence of IRIS served as controls for the clinical findings. RESULTS: Recurrence of arthralgia and/or fever allowed a diagnosis of IRIS in 5/22 patients. One patient died. Previous immunosuppressive therapy was found in all patients with IRIS but only in 7/17 controls (Fisher test, p=0.039). Age at diagnosis and diagnostic delay were higher in patients with IRIS compared to controls. However, statistical significance was not reached. CONCLUSIONS: IRIS is a frequent complication of Whipple's disease and it can be fatal. The risk of IRIS is greatly increased in patients previously treated with immunosuppressive therapy.

A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life.

A dietary interview performed by expert personnel is the best method to check whether patients with coeliac disease follow a strict gluten-free diet (GFD). We previously developed a score based on four fast and simple questions that can be administered even by non-expert personnel. The aim of the present study is to verify the reliability of our questionnaire in a new cohort of patients. The questionnaire has a five-level score. From March 2008 to January 2011, the questionnaire was administered to 141 coeliac patients on a GFD, who were undergoing re-evaluation. The score obtained was compared with persistence of both villous atrophy and endomysial antibodies (EMA). The rate of lower scores was higher among the patients with persistence of either villous atrophy (Fisher's exact, P < 0·001; test for trend, P < 0·001) or positive EMA (Fisher's exact, P = 0·001; test for trend, P = 0·018). Given that the coeliac patients have been well instructed on what a GFD means and on how to follow it, our questionnaire is a reliable and simple method to verify compliance to a GFD.

Are we not over-estimating the prevalence of coeliac disease in the general population?

Until the 1980s, coeliac disease was considered to be a rare disease, but in the 1990s it became clear that it was a frequent condition. Recently, it was suggested to affect 1 out of 100 subjects in the Western world. To understand what the true prevalence of coeliac disease is in the general population, we conducted a systematic review of published papers. The overall prevalence of coeliac disease in the general population appears to be around 1/160 (6.2‰), but this figure varies widely according to the diagnostic criteria used in the original papers. Prevalence obtained with tissue transglutaminase antibodies only was markedly higher than that obtained through a histological diagnosis. We conclude that the prevalence of coeliac disease in the general population has been over-estimated. This is mainly due to tissue transglutaminase antibodies being used as the only diagnostic tool.