Kamran Rostami

Spectrum of gluten-related disorders: consensus on new nomenclature and classification

A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching

Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice

2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.

Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria.

OBJECTIVE:We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives.METHODS:The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2–76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy).RESULTS:The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA.CONCLUSIONS:Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.

HIGH PREVALENCE OF COELIAC DISEASE IN APPARENTLY HEALTHY IRANIAN BLOOD DONORS

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.

The relationship between anti-endomysium antibodies and villous atrophy in coeliac disease using both monkey and human substrate.

Background/objective Studies about the prevalence of coeliac disease in countries in western Asia are scarce and there is no study on the prevalence of coeliac disease in Iran. The aim of this study was to determine the prevalence of coeliac in healthy, Iranian, blood donors. Study design and methods Blood samples were obtained from 2000 apparently healthy blood donors (1580 males, 420 females; mean age 35.5 years, range 18‐65 years) at the Tehran Blood Donation Centre during a 4 month period from November 1998 through February 1999. Total serum IgA was measured in all donors, and IgA deficient cases were excluded. All cases were analysed for IgA anti‐gliadin (AGA) by an ELISA test and those with positive results were tested for IgA anti‐endomysium antibody (EMA) using immunofluorescence. All donors who had a positive serology for both AGA and EMA underwent small intestinal biopsy. The biopsy samples were classified according to revised Marsh criteria (UEGW 2001). Results Forty‐nine cases showed positive IgA AGA (38 males and 11 females, mean age 38.6 years). Of the 49 AGA positive cases 12 were EMA positive. All subjects with positive serology (both AGA and EMA) were found to have small bowel biopsies compatible with gluten sensitive enteropathy. Three of 12 had Marsh I, 4/12 Marsh II and 5/12 showed a Marsh IIIa lesion. Conclusion The minimum prevalence of gluten sensitivity among apparently healthy urban Iranian blood donors is 1/166. Further epidemiological studies in adults from the general population and in high risk groups seems indicated.

When is a coeliac a coeliac

BACKGROUND/OBJECTIVE Circulating antibodies offer a noninvasive diagnostic screening test in patients with coeliac disease with severe histopathological abnormalities. This study assesses for the first time the sensitivity and reliability of anti-endomysium in screening for coeliac disease in patients with milder forms of villous atrophy using human umbilical cord and monkey ileum. MATERIALS AND METHODS Serum from 124 adults and children > 2 years old including 33 patients with coeliac disease on a gluten-free diet and 91 patients referred to the laboratory for screening was studied. The presence of IgA-anti-gliadin (AGA) (ELISA) and IgA-anti-endomysium (EMA) was detected in the serum using monkey ileum and human umbilical cord (HUC) substrates. Patients with abnormal serology results or severe clinical complaints were invited to attend for a small-bowel biopsy. The prevalence of EMA detected on monkey ileum and HUC was compared with the histopathological features of coeliac disease at presentation. Fifty-three of the 91 patients screened for coeliac disease underwent a small intestinal biopsy. RESULTS Twenty-three of the 91 patients suspected of having coeliac disease had coeliac disease. The EMA test was positive in 18 of 23 using both monkey ileum and HUC (sensitivity 78%). Partial villous atrophy (PVA) was seen in four of the five EMA-negative patients, and subtotal/total villous atrophy (SVA/TVA) was demonstrated in 18 of the 23 cases with positive EMA. Both substrates detected identical positive cases. There was an excellent concordance between EMA sensitivity evaluated on HUC and those on monkey ileum. One patient was EMA-negative on monkey ileum but positive on HUC and one patient who was EMA-positive on monkey ileum was EMA-negative on HUC. Only one of 33 coeliac disease patients on gluten-free diet for more than one year with persisting TVA had positive EMA. The rest of the cases had a negative EMA on both HUC and monkey ileum. CONCLUSION A negative result for EMA in coeliac disease patients with a normal IgA value does not exclude the diagnosis of coeliac disease. A positive EMA is seen mostly in those coeliac disease patients with severe tissue damage (SVA/TVA). EMA has a low sensitivity in coeliac disease patients with PVA in spite of use of different substrates.

SAT and serology in adult coeliacs, seronegative coeliac disease seems a reality

It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgement regarding the propriety of any specific guideline must be made by the physician in light of all the circumstances presented by the individual patient.

Microscopic enteritis: Bucharest consensus

UNLABELLED The aim of this study was to assess the correlation of sugar absorption test (SAT) using Lactulose/Mannitol/Sucrose (LMS), with IgA-endomysium (EMA), and IgA-gliadin (AGA) antibodies in relation to the severity of the intestinal mucosal damage in adult coeliacs. We have differentiated the Marsh classification in partial villous atrophy (VA) (III a), subtotal VA (III b), and total VA (III c). Twenty-nine untreated adults coeliacs, with a mean age of 47 years, range 20-76 yrs were studied over 3 years. SAT, IgA-AGA and IgA EMA were performed in 29 consecutive coeliac patients with villous atrophy on a gluten containing diets. RESULTS Histopathological evaluation of small intestinal mucosa showed a partial VA in 14/29, subtotal VA in 10/29 and total VA in 5/29. All coeliacs with total VA had positive EMA (5/5 100%). However in coeliacs with partial VA sensitivity of EMA was poor (4/14 29%). Sensitivity of EMA in patients with subtotal VA was 50% (5/10). AGA was raised in 3/14 (21%), 6/10 (60%), and in 4/5 (80%) coeliacs with partial, subtotal and total VA respectively. AGA was raised in 13/29 (sensitivity 45%). SAT was abnormal in 26/29 (sensitivity: 89%). One patient had abnormal SAT, EMA and AGA. Eleven of 29 patients (38%) were negative for AGA and EMA, but SAT was abnormal in 10 of them. One patient was positive for EMA, negative for AGA, normal for SAT. EMA and/or AGA were positive in 18/29 (sensitivity 62%). Our study suggests that negative predictive value of serology should be interpreted cautiously since coeliacs with partial VA are negative in serology. Over the last ten years SAT and EMA have been accepted as screening tools for CD. SAT seems to be more sensitive than serology. However there is no standardized agreement in the literature for serology and SAT. A combination of SAT and serology may provide a good sensitivity in order to detect that subgroup of coeliacs with milder histopathological abnormality.

Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial

Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

EPIDEMIOLOGY OF CELIAC DISEASE IN IRAN: A REVIEW

Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.