A. Marchese

A gluten-free diet score to evaluate dietary compliance in patients with coeliac disease.

A dietary interview performed by expert personnel is considered to be the most appropriate tool to check whether patients with coeliac disease follow a strict gluten-free diet. However, we currently have no straightforward and non-subjective method for performing such a dietary interview. We therefore developed a fast questionnaire based on four simple questions with a five-level score (0-IV). To verify whether our questionnaire is an efficient tool, we applied it to 168 coeliac patients (126 females and 42 males; mean age 42.4 (SD 12.9) years) on a gluten-free diet (median 82, 25th-75th percentile 50-108, range 15-389 months). The score we obtained was compared with the persistence of both villous atrophy and endomysial antibodies while on a gluten-free diet. A comparison with survival of the patients was also performed. Patients were interviewed over the phone by non-expert personnel. The questionnaire was completed in less than 1 min. The lowest results were significantly more frequent among the patients with a persistence of both villous atrophy and positive endomysial antibodies. Death risk was also significantly correlated with the lowest score results. We conclude that our questionnaire is a reliable and simple method of verifying compliance with a gluten-free diet.

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 (Fishers exact, P < 0·001; test for trend, P < 0·001) or positive EMA (Fishers 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.

Clinical response to gluten withdrawal is not an indicator of coeliac disease

Objective. Although the diagnosis of coeliac disease requires specific histological and serological findings, patients considered to be affected by coeliac disease only on the basis of clinical improvement after gluten withdrawal are commonly referred to our outpatient clinic. The objective of this study was to investigate whether the clinical response of gastrointestinal symptoms to gluten withdrawal and subsequent dietary re-introduction could be an indicator of the presence of coeliac disease. Material and methods. From December 1998 to January 2007, 180 patients on a gluten-free diet because of a diagnosis of coeliac disease not based on proper diagnostic criteria came to our out-patient clinic. In 112 of these patients, gluten was re-introduced into their diet. Subsequent duodenal biopsies and endomysial antibodies confirmed the diagnosis of coeliac disease in 51 of them. The relationship between improvement/worsening of symptoms and withdrawal/re-introduction of dietary gluten was analysed. Results. Gastrointestinal symptoms improved in 64.7% of coeliac patients and 75.0% of non-coeliac patients after gluten withdrawal (χ2 test, p=NS). Gluten re-introduction was followed by clinical exacerbation in 71.4% of coeliac patients and 54.2% of non-coeliac patients (χ2 test, p=NS). The positive predictive value for clinical improvement after gluten withdrawal was 36%; the positive predictive value for clinical exacerbation after gluten re-introduction was 28%. Conclusions. Clinical response to either withdrawal or re-introduction of dietary gluten has no role in the diagnosis of coeliac disease.

The significance of duodenal mucosal atrophy in patients with common variable immunodeficiency: a clinical and histopathologic study.

Gastrointestinal manifestations and villous atrophy can be seen in patients with common variable immunodeficiency (CVID). In some patients, infectious agents may be responsible, whereas in others, celiac disease (CD) may be the cause. In this study, we investigate the causes and the histopathologic features seen in patients with CVID. Eleven patients with CVID and villous atrophy underwent duodenal biopsies, human leukocyte antigen (HLA) typing, and testing for all celiac antibodies. Fifteen patients with CVID and normal villi and 6 patients with CD but without CVID served as controls. Histologic response to a gluten-free diet (GFD) allowed a diagnosis of CD in 3 of 11 patients. In the remaining 8, the lack of a histologic response to a GFD or HLA typing excluded CD. Celiac antibodies gave conflicting results and were of no help. Polymorphonuclear infiltrates and lesions like graft-versus-host disease are seen more often in flat mucosa unresponsive to a GFD. However, the specificity of these findings remains to be determined and response to a GFD remains the only diagnostic criteria for CD in these patients. Villous atrophy was gluten-sensitive in 3 of 11 patients with CVID. It was not related to gluten-responsive CD in most patients.

Prevalence and natural history of potential celiac disease in adult patients

Abstract 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.

Influence of HLA-DQ2 and DQ8 on severity in celiac Disease.

Background HLA-DQB1*02 homozygosity was shown to be more common in patients with complicated rather than uncomplicated celiac disease (CD). Goals To study HLA-DQA1 and DQB1 profile in adult patients with different forms of CD, including patients with complicated and potential CD, the most affected and the most preserved histologic end of the pathologic celiac spectrum. Study HLA-DQA1 and DQB1 molecular typing was performed in 218 adult CD patients (169 with uncomplicated CD, 27 with complicated CD, and 22 with potential CD) and 224 healthy stem cell donors. HLA-DQA1 and DQB1 gene polymorphism was analyzed using polymerase chain reaction sequence-specific primers and/or reverse polymerase chain reaction sequence-specific oligonucleotides techniques. Results As expected, the frequency of HLA-DQB1*02 allele, DQB1*02 homozygosity, and DQB1*0302 gene were statistically different in the 4 groups. However, multivariate analysis demonstrated that patients with potential CD have a higher frequency of both HLA-DQB1*0302 and HLA-DQB1*0603 alleles and a reduced frequency of DQB1*02 homozygosity compared with patients with uncomplicated and complicated CD. Conclusions The increased frequency of DQB1*0302 and the reduced frequency of DQB1*02 homozygosity in potential CD is consistent with the idea that different clinical/pathologic evolutions might be related to different immunogeneses. This could be clinically relevant in the future.

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.

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

INTRODUCTION Whipples 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 Whipples disease itself. Very recently, it has been recognised as a complication of Whipples 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 Whipples disease. METHODS Evidence of IRIS was retrospectively revaluated in the clinical notes of 22 patients with Whipples 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 Whipples disease and it can be fatal. The risk of IRIS is greatly increased in patients previously treated with immunosuppressive therapy.

PROgnosticating COeliac patieNts SUrvivaL: the PROCONSUL score.

Introduction It has been shown that mortality rates of coeliac patients correlate with age at diagnosis of coeliac disease, diagnostic delay for coeliac disease, pattern of clinical presentation and HLA typing. Our aim was to create a tool that identifies coeliac patients at higher risk of developing complications. Methods To identify predictors of complications in patients with coeliac disease, we organised an observational multicenter case-control study based on a retrospective collection of clinical data. Clinical data from 116 cases (patients with complicated coeliac disease) and 181 controls (coeliac patients without any complications) were collected from seven European centres. For each case, one or two controls, matched to cases according to the year of assessment, gender and age, were selected. Diagnostic delay, pattern of clinical presentation, HLA typing and age at diagnosis were used as predictors. Results Differences between cases and controls were detected for diagnostic delay and classical presentation. Conditional logistic models based on these statistically different predictors allowed the development of a score system. Tertiles analysis showed a relationship between score and risk of developing complications. Discussion A score that shows the risk of a newly diagnosed coeliac patient developing complications was devised for the first time. This will make it possible to set up the follow-up of coeliac patients with great benefits not only for their health but also for management of economic resources. Conclusions We think that our results are very encouraging and represent the first attempt to build a prognostic score for coeliac patients.

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.