P.I. Bianchi

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.

The impact of misdiagnosing celiac disease at a referral centre

In the past few years, the number of celiac disease diagnoses not confirmed at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, a tertiary referral centre, was particularly high. Therefore, a decision was made to investigate the reasons why these diagnoses were wrong and by whom they had been made. The clinical histories of all celiac patients referred to the centre were re-evaluated. Between December 1998 and January 2007, 614 patients who were diagnosed at other institutions and presumed to be affected by celiac disease attended the tertiary referral outpatient clinic. The histological and serological results allowed for confirmation the diagnosis in 434 patients. In the remaining 180 patients, the initial diagnosis of celiac disease could not be confirmed; therefore, the patients were re-investigated. After re-evaluation, the diagnosis of celiac disease was confirmed in only 61 of these 180 cases. The reasons for incorrect initial diagnosis were analyzed. A mere 80% correct diagnosis rate is a very disappointing result. Although it should be obvious that celiac disease must be investigated with duodenal biopsies and celiac antibody testing, this well-known strategy is not always followed, probably resulting in an incorrect diagnosis.

The prevalence and the causes of minimal intestinal lesions in patients complaining of symptoms suggestive of enteropathy. A follow-up study.

Aims: Although they are non-specific, minimal intestinal lesions are at the end of the coeliac histological damage spectrum. To investigate whether minimal intestinal lesions in patients without endomysial antibodies are due to coeliac disease, their prevalence, causes and risk of evolving into frank coeliac disease were studied. Methods: From January 2000 to December 2005, 645 duodenal biopsies were performed. In 209 patients, duodenal biopsies were performed independently of endomysial antibody results. Clinical data and HLA-typing of all the patients negative to endomysial antibodies but with minimal mucosal lesions were re-evaluated. Three years later, they were offered to be seen again, and further investigations were proposed. Results: 14 out of 209 patients had minimal mucosal lesions and negative endomysial antibodies. Two patients were lost to follow-up; in 7/12 patients, symptoms and histological lesions were due to a different condition, not related to coeliac disease. In 11/12 patients, HLA-typing made diagnosis of coeliac disease very unlikely. Only one patient was on a gluten-free diet because of gluten-sensitive symptoms and was DQ2+/DQ8+. Conclusions: Minimal duodenal lesions in patients negative to endomysial antibodies are rare and are likely to be due to conditions unrelated to coeliac disease.

IgA anti‐epidermal transglutaminase autoantibodies: a sensible and sensitive marker for diagnosis of dermatitis herpetiformis in adult patients

Background  Dermatitis herpetiformis (DH) is a rare gluten‐sensitive blistering itchy skin disease, strictly related to coeliac disease (CD). Direct immunofluorescence, demonstrating IgA granular deposits localized either in the dermal papillae or along the dermo‐epidermal junction, is currently the gold standard for diagnosis of DH. It has been shown that DH immunocomplexes contain epidermal transglutaminase (eTG) and that sera from patients with DH contain antibodies specifically directed against eTG.

Carriage of CARD15 variants and smoking as risk factors for resective surgery in patients with Crohn's ileal disease

Background:  It is controversial whether CARD15 variants are truly associated with a more severe form of Crohns disease. The relative role of CARD15 genotype and smoking in Crohns disease progression is also debated.