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Our understanding of the pathophysiology of celiac disease has progressed greatly over the past 25 years; however, some fallacies about the clinical characteristics and management persist. Worldwide epidemiologic data are now available showing that celiac disease is ubiquitous. An elevated body mass index is common at the time of the diagnosis. The gluten-free diet (GFD) is an imperfect treatment for celiac disease; not all individuals show a response. This diet is widely used by people without celiac disease, and symptomatic improvement on a GFD is not sufficient for diagnosis. Finally, the GFD is burdensome, difficult to achieve, and thus has an incomplete efficacy, opening exciting opportunities for novel, nondietary treatments., (Copyright © 2021 by The American College of Gastroenterology.)

Introduction: Many patients with celiac disease (CD) experience persistent symptoms despite adhering to the gluten-free diet. Different studies have assessed the use of probiotics as an adjuvant treatment for CD. We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal (GI) symptoms and quality of life (QOL) in patients with CD., Methods: We searched EMBASE, MEDLINE, CINAHL, Web of Science, CENTRAL, and DARE databases up to February 2019 for randomized controlled trials (RCTs) evaluating probiotics compared with placebo for treating CD. We collected data on GI symptoms, QOL, adverse events, serum tumor necrosis factor-α, intestinal permeability, and microbiota composition., Results: We screened 2,831 records and found that 7 articles describing 6 RCTs (n = 279 participants) were eligible for quantitative analysis. Probiotics improved GI symptoms when assessed by the GI Symptoms Rating Scale (mean difference symptom reduction: -28.7%; 95% confidence interval [CI] -43.96 to -13.52; P = 0.0002). There was no difference in GI symptoms after probiotics when different questionnaires were pooled. The levels of Bifidobacteria increased after probiotics (mean difference: 0.85 log colony-forming units (CFU) per gram; 95% CI 0.38-1.32 log CFU per gram; P = 0.0003). There were insufficient data on tumor necrosis factor-a levels or QOL for probiotics compared with placebo. No difference in adverse events was observed between probiotics and placebo. The overall certainty of the evidence ranged from very low to low., Discussion: Probiotics may improve GI symptoms in patients with CD. High-quality clinical trials are needed to improve the certainty in the evidence (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B595).

Introduction: Celiac disease (CD) is common, affecting approximately 1% of the population. The cornerstone of management is a gluten-free diet, with dietetic advice being the key to aiding implementation. The aim of the study was to assess group clinics in comparison with traditional individual appointments., Methods: Patients with a new diagnosis of CD, confirmed histologically, were prospectively recruited over 18 months in Sheffield, United Kingdom. Patients received either a group clinic or traditional one-to-one appointment, led by a dietitian. Quality-of-life questionnaires were completed at baseline, as well as biochemical parameters being recorded. Patients were followed up at 3 months, where adherence scores were assessed as well as biochemical parameters and quality of life questionnaires being completed., Results: Sixty patients with CD were prospectively recruited and received either an individual (n = 30) or group clinic (n = 30). A statistically significant reduction in tissue transglutaminase was noted following group clinics (mean 58.5, SD 43.4 U/mL vs mean 13.2, SD 5.7 U/mL, P < 0.01). No significant differences in baseline and follow-up biochemical parameters between one-to-one and group clinics were noted. At follow-up, there was no statistically significant difference between mean gluten-free diet adherence scores (mean 3.1, SD 0.4 vs mean 3.1, SD 0.7, P = 0.66) between one-to-one and group clinics., Discussion: This first study assessing group clinics in CD demonstrates they are as effective as traditional one-to-one clinics, with the added benefits of peer support and greater efficiency, with an estimated 54% reduction of dietetic resources.

Objectives: Response to gluten challenge (GC) is a key feature in diagnostic algorithms and research trials in celiac disease (CD). Currently, autoantibody titers, late responders to GC, and invasive duodenal biopsies are used to evaluate gluten responsiveness. This study investigated the accuracy of serum intestinal-fatty acid binding protein (I-FABP), a marker for intestinal epithelial damage, to predict intestinal damage during GC in patients with CD., Methods: Twenty adult CD patients in remission underwent a two-week GC with 3 or 7.5 g of gluten daily. Study visits occurred at day -14, 0, 3, 7, 14, and 28. Serum I-FABP, antibodies to tissue transglutaminase (tTG-IgA), deamidated gliadin peptides (IgA-DGP), and anti-actin (AAA-IgA) were assessed at each visit. Villous-height to crypt-depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count were evaluated at day -14, 3, and 14. Forty-three CD-serology negative individuals were included to compare serum I-FABP levels in CD patients on a gluten-free diet (GFD) with those in healthy subjects., Results: Serum I-FABP levels increased significantly during a two-week GC. In contrast, the most pronounced autoantibody increase was found at day 28, when patients had already returned to a GFD for two weeks. IgA-AAA titers were only significantly elevated at day 28. I-FABP levels and IEL count correlated at baseline (r=0.458, P=0.042) and at day 14 (r=0.654, P=0.002) of GC. Neither gluten dose nor time on a GFD influenced I-FABP change during GC., Conclusions: Serum I-FABP levels increased significantly during a two-week GC in adult CD patients and correlated with IEL count. The data suggest that serum I-FABP is an early marker of gluten-induced enteropathy in celiac patients and may be of use in both clinical and research settings.

Celiac disease (CeD) is one of the most common immune-mediated diseases. Symptoms and disease activity are incompletely controlled by the gluten-free diet, which is currently the only available therapy. Although no therapies are yet approved, there is a growing field of candidates and an improving understanding of the regulatory pathway. In this review, we briefly discuss the epidemiology, pathophysiology, and current treatment paradigm for CeD. We also review the major classes of therapies being considered for CeD and discuss extensively what is known and can be surmised regarding the regulatory pathway for approval of a CeD therapeutic. The coming years will see an increasing number and diversity of potential therapies entering clinical trials and hopefully the first approved agents targeting this significant unmet medical need. Although biomarkers including histology and serology will always be important in therapeutic clinical trials, they currently lack the necessary evidence linking them to improved patient outcomes required for use as primary outcomes for drug approval. For this reason, patient-reported outcomes will likely be primary end points in Phase III CeD trials for the foreseeable future.

Objectives: Non-coeliac gluten sensitivity (NCGS) refers to patients with primarily gastrointestinal symptoms without enteropathy that symptomatically benefit from gluten-free diet (GFD). Little is known about its pathophysiology, propensity to neurological manifestations, and if these differ from patients with coeliac disease (CD). We investigated the clinical and immunological characteristics of patients presenting with neurological manifestations with CD and those with NCGS., Methods: We compared clinical, neurophysiological, and imaging data of patients with CD and NCGS presenting with neurological dysfunction assessed and followed up regularly over a period of 20 years., Results: Out of 700 patients, 562 were included. Exclusion criteria included no bowel biopsy to confirm CD, no HLA type available, and failure to adhere to GFD. All patients presented with neurological dysfunction and had circulating anti-gliadin antibodies. Out of 562 patients, 228 (41%) had evidence of enteropathy (Group 1, CD) and 334 (59%) did not (Group 2, NCGS). The most common neurological manifestations were cerebellar ataxia, peripheral neuropathy, and encephalopathy. There was a greater proportion of patients with encephalopathy in Group 1 and with a greater proportion of neuropathy in Group 2. The severity of ataxia did not differ between the two groups. Patients in Group 1 had more severe neuropathy. All patients from both groups responded to gluten-free diet. Anti-tissue transglutaminase (TG2) antibodies were found in 91% of patients in Group 1 and in 29% of patients in Group 2. Comparison between those patients in Group 2 with HLA-DQ2/DQ8 and those without as well as those with positive TG2 compared with those with negative TG2 antibodies identified no differences within these subgroups. Serological positivity for TG6 antibodies was similar in the two groups (67 and 60%)., Conclusions: The neurological manifestations of CD and NCGS are similar and equally responsive to a GFD suggestive of common pathophysiological mechanisms.

Objectives: The Marsh classification is a semiquantitative method for the diagnosis and monitoring of changes in duodenal biopsies in celiac disease. We have explored the possibility that quantitative changes in villous area and crypt length (morphometry) may provide better information on changes in duodenal morphology, particularly after the introduction of a gluten-free diet., Methods: We measured villous height, apical and basal villous widths, and crypt length in 57 adults with celiac disease and 83 control subjects. Villous area was calculated as a trapezoid approximation. Serial changes in villous area and crypt length were determined at regular intervals for up to 4 years after the introduction of a gluten-free diet. Morphometric changes were also correlated with Marsh grade, self-reported adherence to a gluten-free diet, and changes in celiac serology., Results: The gluten-free diet resulted in a progressive increase in villous area and a progressive decrease in crypt length. Morphometric improvement reached a plateau after 6-12 months with mean villous area attaining a value approximately half that of control subjects. Morphometric data were more sensitive than Marsh grade. Improvement in morphometric indices was significantly associated with the disappearance of anti-endomysial IgA antibody but not with dietary compliance., Conclusions: Morphometry is a sensitive way to document changes in duodenal biopsies in celiac disease. In adults treated with a gluten-free diet, it is uncommon for villous area to return to values observed in control subjects, but morphometric improvement is associated with the disappearance of anti-endomysial IgA antibody.

Objectives: Nonclassical major histocompatibility class I HLA-G antigen is a tolerogenic molecule that inhibits lytic activity of natural killer (NK) cells and cytotoxic T lymphocytes. Because of its immunomodulatory and tolerogenic properties, HLA-G molecules may have a role in celiac disease (CD). We analyzed the HLA-G 14 bp deletion/insertion polymorphism, known to have a functional effect on mRNA stability, in a group of 522 CD patients, stratified for the presence of HLA-DQ2 genotype, and 400 healthy individuals to evaluate the possible effect of the polymorphism on the risk to develop the disease., Methods: HLA-G 14 bp deletion/insertion polymorphism (rs1704) was detected by polymerase chain reaction and double-checked by direct sequencing., Results: The 14 bp inserted (I) allele and the homozygous I/I genotype were significantly more frequent in CD patients than in healthy controls. The presence of I allele was associated with an increased risk of CD (OR 1.35) and the effect of I allele was consistent with a recessive genetic model (P<0.001)., Conclusions: Our results also indicate that the effect of the HLA-G D/I polymorphism is restricted for HLA-DQ2, and not simply due to the presence of linkage disequilibrium with the major known risk factor; moreover we found that the presence of the I allele confers an increased risk of CD in addition to the risk conferred by HLA-DQ2 alone and that subjects that carry both DQ2 and HLA-G I alleles have an increased risk of CD than subjects that carry DQ2 but not the I allele.

Objectives: The enteropathy associated with common variable immunodeficiency (CVID) is poorly characterized, and its possible relationships with well-defined causes of enteropathy, such as celiac sprue (CS), remain debated. We aimed to assess the clinical and histopathological features of the enteropathy associated with CVID., Methods: The medical files of 50 CVID patients with gastrointestinal symptoms were analyzed retrospectively. Histological, phenotypic, and molecular analysis of intestinal endoscopic specimens was centrally performed., Results: Chronic diarrhea was the most frequent gastrointestinal symptom (92%), and biological evidence of malabsorption was observed in 54% of patients. Chronic gastritis associated or not with pernicious anemia and microscopic colitis were the most frequently observed histopathological features in gastric and colonic mucosa, respectively. Small-bowel biopsies available in 41 patients showed moderate increase in intestinal intraepithelial lymphocytes in 31 patients (75.6%) and villous atrophy in 21 patients (51%). Distinctive features from CS were a profound depletion in plasma cells and follicular lymphoid hyperplasia. Presence of peripheral blood CD8+ hyperlymphocytosis was predictive of intestinal intraepithelial hyperlymphocytosis. Intravenous (i.v.) immunoglobulin (Ig) therapy had no effect on enteropathy-related symptoms. Gluten-free diet improved only two out of 12 patients with villous atrophy, whereas all patients (7/7) responded to steroid therapy., Conclusions: Several distinctive features differentiate CVID enteropathy from other causes of enteropathy including CS. Replacement i.v. Ig therapy is insufficient to improve gastrointestinal symptoms. Steroids are effective in reducing inflammation and restoring mucosal architecture.

Objectives: Our aim was to explore the diagnostic value of fasting citrulline concentrations to detect decreased intestinal energy absorption in patients with recently diagnosed celiac disease (CeD), refractory celiac disease (RCeD), and short bowel syndrome (SBS). Decreased intestinal energy absorption is regarded a marker of intestinal failure., Methods: Fasting plasma citrulline concentrations were determined by high performance liquid chromatography (HPLC) in a prospective study of 30 consecutive adult patients (15 CeD, 9 RCeD, and 16 SBS) and 21 healthy subjects. Intestinal energy absorption capacity using bomb calorimetry was determined in all patients and healthy subjects and was regarded as the gold standard for intestinal energy absorption function., Results: The mean fasting plasma citrulline concentration was lower in RCeD patients than in healthy subjects (28.5+/-9.9 vs 38.1+/-8.0 micromol/L, P<0.05) and CeD patients (28.5+/-9.9 vs 38.1+/-6.4 micromol/L, P<0.05), however, clearly within reference values. The mean intestinal energy absorption capacity was lower in SBS patients than in healthy subjects (64.3+/-18.2 vs 90.3+/-3.5%, P<0.001), CeD patients (64.3+/-18.2 vs 89.2+/-3.4%, P<0.001), and the RCeD group (64.3+/-18.2 vs 82.3+/-11.7%, P<0.01). No relation was observed between fasting plasma citrulline concentration and intestinal energy absorption capacity (Pearson r=0.09, P=0.56). The area under the ROC curve for fasting plasma citrulline to detect decreased intestinal energy absorption capacity (i.e., <85%) was 0.50., Conclusion: Fasting plasma citrulline concentrations have poor test characteristics for detection of decreased intestinal energy absorption capacity in patients with enterocyte damage.

Unlabelled: BACKGROUND Causes of chronic watery diarrhea are multiple. There is not definite scientific evidence about AND AIMS: which are the recommended explorations to be performed in the diagnostic workup of patients with functional diarrhea. The aim was to assess prospectively the presence of gluten-sensitive enteropathy, bile acid malabsorption, and sugar malabsorption in consecutive patients with chronic watery diarrhea of obscure origin fulfilling Rome II criteria of functional disease., Methods: A total of 62 patients with chronic watery diarrhea, defined as more than 3 loose or liquid bowel movements a day for at least 4 wk and a stool weight >200 g/day were included. The following tests were performed: (a) HLA-DQ2/DQ8 genotyping, and if positive, endoscopic biopsies from distal duodenum were obtained, and intestinal damage assessed; (b) SeHCAT (Se-homotaurocholate) abdominal retention test; (c) small bowel follow-through; and (d) hydrogen breath test (lactose, fructose + sorbitol). Gluten- or sugar-free diet, or cholestyramine was administered according to results. Functional disease was diagnosed if all tests performed were normal or if either there was no response to specific therapy or diarrhea relapsed during a 12-month follow-up., Results: Bile acid malabsorption was considered to be the cause of diarrhea in 28 (45.2%) patients, sugar malabsorption in 10 (16.1%), gluten-sensitive enteropathy in 10 (16.1%), and both bile acid and sugar malabsorption in 2 patients. Twelve (19.4%) patients remained without a specific diagnosis and were considered as functional bowel disease. Diarrhea stopped in the 50 patients after specific treatment, decreasing the daily stool number from 5.4 +/- 0.3 to 1.5 +/- 0.1 (P < 0.0005), without relapse after the 12-months follow-up., Conclusions: The diagnosis of functional disease in patients with chronic watery diarrhea should be performed with caution since in most cases there is an organic cause that justifies diarrhea.

Objectives: New studies indicate that body mass index (BMI) may influence gut transit. We studied gut transit and BMI in patients with celiac disease before and after treatment., Methods: Twenty-seven (16 female) patients with untreated celiac disease were included for detailed gastrointestinal transit measurement and calculation of BMI. Ten patients (5 female) were also studied after dietary treatment. A newly developed radiological transit procedure was used. Eighty-three healthy subjects were used as controls., Results: In untreated male patients BMI was significantly reduced compared to healthy males, and small bowel transit time (SBTT) was significantly longer compared with healthy males, 3.9 (1.2-5.5) versus 2.5 h (1.4-4.3), median and percentile 10 and 90, respectively, and p= 0.04. In the 10 men and women with repeated measurements, BMI increased significantly and small bowel transit accelerated after treatment and was 3.6 h (1.7-5.5) before treatment and 2.3 h (0.7-4.0) after treatment, and p= 0.007. In women, BMI did not differ significantly between untreated patients and healthy subjects, and 31% of the female patients were overweight. Small bowel transit was significantly faster in untreated female patients who were overweight compared with lean female patients., Conclusion: Small bowel transit seems to be delayed in lean patients with untreated celiac disease. BMI may have some influence on the variations of small bowel transit before and after treatment.

Objectives: Follow-up of celiac disease diagnosed in childhood is variable or nonexistent after transition to adulthood. Outcome, continuity of care, and adherence to a gluten-free diet are poorly documented. We report a 28-yr follow-up of 50 adults in whom the original childhood diagnosis could be confirmed., Methods: Original pediatric charts were reviewed, and subjects were invited to undergo dietary evaluation, measurement of bone mineral density, and quality-of-life assessment. The mean duration of celiac was 28.5 yr, median 28.7 yr (range 22-45 yr). The mean and median age of the group was 35 yr., Results: Only 22% of patients were enrolled in an adult gastroenterology clinic. Fifty percent were fully compliant with a gluten-free diet; 18% were partially compliant; and 32% were not adhering to diet. The main motivating factor for dietary compliance was avoidance of symptoms rather than avoidance of complications. Eighty-six percent of the females and 21% of the males had iron deficiency. Bone mineral density was subnormal in 32%; 28.9% were osteopenic and 2.6% were osteoporotic. Quality-of-life scores were normal., Conclusions: Most patients diagnosed with celiac in childhood receive no medical or dietary supervision after transition to adulthood. One-third are not compliant with diet; the primary motivating factor for those who do comply is avoidance of symptoms rather than fear of complications. The prevalence of preventable and treatable disorders in these young adults highlights a failure of health services after transition from pediatric to adult health care.

Objectives: Subclinical celiac disease (CD) has been associated with various neurological disorders, the most common being neuropathy and cerebellar ataxia. The aims of the present study were to assess the following: 1) the prevalence of CD in patients affected by migraine; 2) whether there are regional cerebral blood flow abnormalities in migraine patients with CD compared to migraine patients without CD; and 3) the effects of a gluten free diet in migraine patients with CD., Methods: A total of 90 patients affected by idiopathic migraine were enrolled, and 236 blood donors were used as controls. Serum IgG antitransglutaminase (TgA) and IgA antiendomysial (EmA) were measured. In positive cases, diagnosis was confirmed endoscopically. A gluten free diet was started in the patients diagnosed with CD, who were followed for 6 months. A single photon emission CT brain study was performed before and after a gluten free diet., Results: Four of 90 (4.4%; 95% CI = 1.2-11.0) migraine patients were found to have CD compared with 0.4% (95% CI = 0.01-2.3) blood donor controls (p < 0.05). During the 6 months of gluten free diet, one of the four patients had no migraine attacks, and the remaining three patients experienced an improvement in frequency, duration, and intensity of migraine. Single photon emission CT studies showed a regional baseline reduction in brain tracer uptake in all four patients. Such reduction in uptake completely resolved at follow-up., Conclusions: Our results suggest that a significant proportion of patients with migraine may have CD, and that a gluten free diet may lead to a improvement in the migraine in these patients.

Objectives: Previous reports have linked irritable bowel syndrome (IBS) etiologically with various forms of mucosal inflammation, including infectious enterocolitides and inflammatory bowel disease. The mechanism is uncertain but may involve sensitization by inflammatory mediators. The enteropathy of celiac disease has theoretical advantages as a study model because it can be controlled with dietary gluten exclusion; however, whether it also predisposes to functional bowel disorders is unclear. Therefore, we assessed the prevalence of IBS-type symptoms in adult celiac patients and correlated this with dietary compliance with gluten exclusion., Methods: Adult patients (n = 150; 106 women and 44 men) with confirmed celiac disease were randomly selected from a computerized database of >350 patients, and were asked to complete a bowel questionnaire and the Short Form 36 Health Survey (SF-36). The control group (n = 162; 133 women and 29 men) had no history of celiac disease and had similar mean age and sex profile., Results: Of 150 celiac patients reviewed, 30 of 150 (20%) fulfilled the Rome criteria compared with eight of 162 (5%) ontrols. Of the celiac patients 10 of 46 (22%) had partial or no compliance with a gluten-free diet, whereas 20 of 104 patients (19%) adhered to the diet; this difference did not achieve statistical significance. Celiac patients with IBS-type symptoms had a markedly lower quality of life than those without, all eight domains being impaired to a clinically significant extent. Dietary gluten exclusion improved QOL in four of eight scales measured., Conclusions: The hypothesis that mucosal inflammation in celiac disease may have a sensitizing effect or may predispose to IBS-type symptoms is supported by these results. Failure to attain optimal subjective well-being is common in celiac patients, particularly in those with coexisting IBS. Compliance with a gluten-free diet confers some benefit.

Celiac sprue is a common lifelong disorder affecting 0.3-1% of the Western world and causing considerable ill health and increased mortality, particularly from lymphoma and other malignancies. Although high prevalence rates have been reported in Western Europe, celiac sprue remains a rare diagnosis in North America. Whether celiac sprue is truly rare among North Americans or is simply underdiagnosed is unclear, although serological screening of healthy American blood donors suggests that a large number of American celiacs go undiagnosed. Celiac sprue is an elusive diagnosis, and often its only clue is the presence of iron or folate deficiency anemia or extraintestinal manifestations, such as osteoporosis, infertility, and neurological disturbances. The challenge for gastroenterologists and other physicians is to identify the large population of undiagnosed patients that probably exists in the community and offer them treatment with a gluten-free diet that will restore the great majority to full health and prevent the development of complications. The advent of highly sensitive and specific antiendomysium and tissue transglutaminase serological tests has modified our current approach to diagnosis and made fecal fat and D-xylose absorption testing obsolete. A single small bowel biopsy that demonstrates histological findings compatible with celiac sprue followed by a favorable clinical and serological response to gluten-free diet is now considered sufficient to definitely confirm the diagnosis. We review the wide spectrum of celiac sprue, its variable clinical manifestations, and the current approach to diagnosis.

Objective: Early studies revealed that up to 50% of non-atrophic, first-degree relatives of celiac disease patients exhibit features of gluten sensitivity. However, whether these features progress to a fully expressed celiac disease remain partially known. Our aim was to report two new patients resulting from a prospective, long-term surveillance of relatives who were nonatrophic at initial assessment., Methods: After a median time of 86 months (range: 42-102 months) from the baseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte infiltration, and 23 did not. In addition, 11 of 18 had a celiac-like response to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-related serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positive subjects underwent intestinal biopsy., Results: At the end of the study, EmA was positive in only two subjects. Histological examination revealed flat small bowel mucosa in both. At baseline, both cases were EmA-negative and no minor histological changes were observed. One was a woman with positive baseline IgA and IgG AGA and a rectal gluten challenge with a celiac-like response; the other patient has presented only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA DQ2 haplotype., Conclusions: Our data suggest the need to re-evaluate relatives who have been negative on initial screening for celiac disease. Up to now, the progression to severe enteropathy was only observed in relatives who had presented some evidence of gluten sensitivity and the characteristic HLA DQ2 haplotype. Longer longitudinal studies are necessary to obtain definitive conclusions.

Objectives: Although osteopenia and osteoporosis are well-recognized complications of celiac disease, no controlled studies have been done to assess the prevalence of fractures in a large cohort of patients. The objectives of this study were to determine the prevalence of bone fractures and vertebral deformities in celiacs and to analyze the relationship between fractures and clinical data of patients., Methods: We studied 165 patients with a well-established diagnosis of celiac disease. A similar number of age- and gender-matched control subjects with functional GI disorders were evaluated. The design of the study was cross-sectional, with a retrospective historical review through a personal interview of all subjects. All patients underwent bone mineral density measurement by dual-energy, x-ray absorptiometry and spinal x-ray. Vertebral deformities were determined by visual inspection of spinal x-rays and by morphometric analysis., Results: Among celiacs, 41 patients (25%) referred have had from one to five fractures in the peripheral skeleton. On the contrary, only 14 (8%) control subjects experienced fractures. This difference was highly significant (odds ratio, 3.5; 95% confidence interval [CI], 1.8-7.2; p<0.0001). Although inspection of spinal x-rays showed evidence of vertebral deformities in the lumbar spine in only two patients, a more detailed examination of lateral x-rays using morphometric criteria detected lumbar spine vertebral deformities in nine (five also had fractures in the peripheral skeleton) and in four controls (odds ratio, 2.8; 95% CI, 0.7-11.5; p = NS). Eighty percent of fractures were detected before the diagnosis of celiac disease or in patients who were noncompliant with the gluten-free diet; only 7% of patients experienced fractures after starting treatment. Regression analysis adjusted for multiple comparisons showed that patients with fractures were diagnosed with celiac disease later (p<0.06) and remained undiagnosed for more prolonged periods (p<0.05). There was a trend, which did not reach statistical significance, for a lower bone mineral density in the lumbar spine and total skeleton among patients with fractures., Conclusions: This study has demonstrated that patients with celiac disease had a high prevalence of bone fractures in the peripheral skeleton. Most of these events occurred before diagnosis or while patients were noncompliant with gluten-containing diet. Our results suggest that early diagnosis and effective treatment of celiac disease were the most relevant measures to protect patients from the risk of fractures.

Objectives: First-degree relatives of patients with celiac disease are at high risk for developing the disease themselves. Detection of serum antibodies and intestinal permeability tests have been useful to identify candidates for intestinal biopsies. Recently it was demonstrated that abnormal sucrose permeability is a very sensitive marker of active disease. Our objectives in this prospective study were (1) to assess the screening value of permeability tests, and (2) to compare the usefulness of these markers with that of the celiac disease-related serology in screening for celiac disease in a cohort of first-degree relatives of well-known patients., Methods: We performed sugar tests in 66 first-degree relatives of probands. Subjects ingested 450 ml of a solution containing sucrose (100 g), lactulose (5 g), and mannitol (2 g). Subsequently, a complete overnight urine collection was obtained. Measurement of sugars was performed by high-performance liquid chromatography. All relatives were evaluated for antigliadin (type IgA and IgG) and endomysial antibodies and subjects positive for any test underwent intestinal biopsy., Results: Twelve relatives were diagnosed as having small intestinal mucosal atrophy. Increased sucrose permeability was detected in 9 (75%) of these patients. Four false-positive determinations were found but all had gastric erosions, which is known to increase sucrose permeability independently of duodenal damage. Increased lactulose/mannitol ratios were observed in all new celiac patients. An additional nine relatives had positive results; however, four of them did not accept intestinal biopsy and the remaining five did not seem to have histological evidence of disease. Endomysial antibodies were detected in 11 of 12 patients and no false-positive cases were observed. Antigliadin antibodies were 75% sensitive and 88% specific., Conclusions: Our study demonstrated that screening using the endomysial antibody test is highly sensitive and specific for detecting celiac disease; however, almost 10% can be missed. The addition of lactulose/mannitol permeability testing to the screening protocol allowed us to detect all relatives who actually presented with evidence of gluten sensitivity. Sucrose permeability exhibited a lower sensitivity; however, it did detect other endoscopically visible lesions.

Objective: Gallbladder hypomotility in celiac disease has been attributed to decreased cholecystokinin secretion. The possible influence of somatostatin, which inhibits gallbladder motility, however, has never been evaluated. In this study gallbladder emptying and cholecystokinin and somatostatin plasma levels were evaluated in response to a fatty meal in patients with celiac disease at diagnosis and after long-term gluten-free diet and in controls., Methods: Gallbladder volume and plasma levels of cholecystokinin and somatostatin were measured by ultrasonography and radioimmunoassay, respectively, at 0 time and 30, 60, 75, and 90 min after an oral fatty meal (227 kcal, 45% fat) in 10 celiac patients at diagnosis and after 18 months of successful gluten-free diet and in 10 healthy subjects. The pattern of gallbladder emptying was evaluated by mixed factorial analysis of variance and the curve fitting by multiple regression analysis., Results: Patients at diagnosis had significantly greater fasting gallbladder volume and higher somatostatin plasma levels than controls (25.7 +/- SD 9.7 ml vs 16.8 +/- 7.0 ml, p = 0.021 and 9.3 +/- 4.6 vs 4.8 +/- 3.4 pmol/L, p = 0.023, respectively), significantly lower fatty meal-induced gallbladder ejection fraction (55 +/- 11.2% vs 76 +/- 7.2%, p = 0.005), and cholecystokinin peak and smaller area under the cholecystokinin secretion curve (3.1 +/- 2.3 pmol/L vs 10.5 +/- 6.9 pmol/L, p = 0.028 and 157 +/- 142 pmol/L/90 min vs 453 +/- 229 pmol/L/90 min, p = 0.028, respectively). The two groups had a similar emptying pattern (p = 0.8913) expressed by a significant quadratic term of the emptying function (p = 0.0001). The mean overall emptying volume was significantly greater in patients than in controls (p = 0.0007). Gluten-free diet normalized these findings., Conclusions: In patients at diagnosis, elevated somatostatin levels were associated with increased gallbladder fasting volume, whereas decreased cholecystokinin secretion was responsible for the reduced gallbladder emptying. Gluten-free diet reversed these abnormalities.

Objectives: Because there is controversy regarding the prevalence, familial occurrence, and possible factors inducing splenic hypofunction in celiac disease, we have reassessed them in a large series of untreated patients and their first-degree relatives., Methods: Pitted red cell counting was used to measure splenic function and the effect that age at diagnosis has on it, while severity of intestinal lesions and nutritional status were estimated by multiple linear regression analysis. Moreover, serum tuftsin activity was assayed by measuring its ability to stimulate phagocytosis of opsonized Staphylococcus aureus., Results: We found that 32.8% of untreated celiacs and none of their relatives had pitted red cell values in the range of splenic hypofunction (>4%). Only age at diagnosis, but not the other two covariates, was significantly associated with the degree of splenic hypofunction. Tuftsin activity was depressed in celiac disease and this reduction was significantly greater in hyposplenic patients., Conclusions: In celiac disease the prevalence of splenic hypofunction is lower than formerly believed. The duration of preexposure to gluten is a crucial factor for the prevalence and severity of this complication that does not affect celiac relatives. In celiac disease splenic hypofunction is accompanied by a reduced phagocyte activity linked to the decreased release of tuftsin.

Objective: A high prevalence of reflux esophagitis in celiac children and gut motor disorders in adult patients have been described. The aim of this study is to investigate the prevalence of esophageal symptoms and the esophageal motility pattern in adult celiac patients before and after gluten-free diet., Methods: In 22 consecutive adult celiac patients, before and after gluten-free diet, and in controls we calculated an esophageal symptom score regarding heartburn, regurgitation, dysphagia, and chest pain, and performed esophageal manometry using a constantly perfused multilumen catheter., Results: Patients were divided into two groups: with and without steatorrhea. Before gluten-free diet, the prevalence of esophageal symptoms was 45.5 % in all patients, but was significantly higher in patients with steatorrhea than in those without and in 44 control subjects (80% vs 16.7% and 27%, p < 0.05). Lower esophageal sphincter pressure was 17.5+/-5.3 in all patients, but was significantly lower in patients with steatorrhea than in patients without steatorrhea and 11 controls subjects (13.1+/-4.1 vs 21.0+/-2.9 and 20.7+/-3.7 mm Hg (mean+/-SD, p < 0.05). After the diet, the prevalence of esophageal symptoms diminished in all patients (9% vs 45.4%, p < 0.05) and lower esophageal sphincter pressure, measured in 13 patients, increased (19.0+/-3.7 vs 15.7+/-5.3 mm Hg, p < 0.05)., Conclusion: Adult celiac patients with steatorrhea present a higher prevalence of esophageal symptoms and a lowered lower esophageal sphincter pressure compared with celiac patients without steatorrhea and control subjects, but these phenomena can be reverted to control levels by gluten-free diet.

Objective: The aim of this study was to determine the prevalence of steatorrhea in patients with Graves' disease and to assess its significance and correlation with changes in body mass index (BMI), coefficient of fat absorption (COFA), and pancreatic exocrine function in these patients., Methods: Daily dietary fat intake, 24 h fecal fat, COFA, fecal chymotrypsin activity (as an index of pancreatic exocrine function), and total T3, T4, and TSH levels were assessed in 28 patients with active Graves' disease. In 24 patients, reassessment was done after attaining a euthyroid state with carbimazole therapy., Results: In the thyrotoxic state, 13 of 28 patients had steatorrhea, whereas 15 had normal (<6 g/day) fat excretion (11.4 +/- 6.7 g vs 2.9 +/- 0.8 g, p = 0.0007). Daily fat intake, basal BMI, and serum T3 and T4 levels were similar in the steatorrheic and nonsteatorrheic groups. The mean COFA of the steatorrheic group was significantly lower than that of nonsteatorrheic group (91.6% +/- 4.8% vs 97.7% +/- 0.9%, respectively; p = 0.0006). In the steatorrheic group, fat excretion and COFA normalized after attainment of euthyroidism (changes in fat excretion and COFA = 7.3% +/- 6.3 g/day and 7.7% +/- 5.4%, respectively). Fecal chymotrypsin levels were similar in the steatorrheic and nonsteatorrheic thyrotoxics and in 16 healthy control subjects. The levels did not show any significant changes following attainment of euthyroid status., Conclusion: Steatorrhea associated with a decrease in COFA can occur in a reversible manner in 46% of patients with Graves' disease. However, steatorrhea in these patients is not linked with weight loss or with pancreatic exocrine dysfunction.

Background: An association between celiac disease and primary biliary cirrhosis has been reported in a few cases, mainly as individual case reports., Objectives: To screen adult patients with celiac disease for primary biliary cirrhosis and patients with primary biliary cirrhosis for intestinal celiac involvement., Methods: The celiac group consisted of 336 adults (218 women and 118 men; mean age, 36 yr; range 18-74 yr) with celiac disease diagnosed by serological and histological tests, 38 with newly diagnosed celiac disease and 298 with previously diagnosed celiac disease who were consuming a gluten-free diet. The mean follow-up period was 6 yr (range, 1-16 yr). Liver function parameters and autoantibody levels were determined, and, when indicated, histological tests were performed. The biliary cirrhosis group consisted of 65 subjects (58 women and seven men) (mean age, 59 yr; range, 35-67 yr) with primary biliary cirrhosis diagnosed 1-17 years previously (mean, 7 yr) on the basis of the usual biochemical, serological, and histological criteria. Antigliadin and antiendomysium antibody levels were determined, and two biopsy specimens from the distal duodenum obtained during endoscopy were evaluated., Results: In patients with celiac disease, impairment of liver function was frequently found at diagnosis (16 of 38, or 44%), but primary biliary cirrhosis was diagnosed in only one case. In patients with primary biliary cirrhosis, no cases of celiac disease, as currently defined, were found., Conclusions: Our findings indicate that celiac disease and primary biliary cirrhosis are rarely associated and support the hypothesis that the intestinal lesions per se are not responsible for the liver disease.

Objectives: The aim of the study was to establish whether body composition in patients with celiac disease is normal and influenced by the age at diagnosis or by the duration of the gluten free diet., Methods: A group of 66 children with celiac disease and 76 healthy controls were studied by dual energy x-ray absorptiometry. We compared celiac patients with the control group, and within the celiac disease group, we compared patients with different age at diagnosis (28 diagnosed in the first 24 months vs 38 later) and with different duration of the diet (16 in gluten free diet for less than 12 months, 11 for less than 24 months, and 39 for more than 24 months)., Results: Overall we did not find any significant difference in body composition between overall celiac patients and controls. However the fat mass, the body mass index, and the spine bone mineral density values in late diagnosed celiac patients were significantly lower than in early diagnosed patients (significance values were p < 0.009; p < 0.002; p < 0.002, respectively). Patients on diet for less than 12 months showed significantly lower bone mineral content and density than those on diet for more than 24 months (significance values were, respectively, p < 0.011 and p < 0.022). Spine mineral density was the only parameter significantly influenced both by age at diagnosis (p < 0.03) and duration of gluten free diet (p < 0.008)., Conclusions: Only an early diagnosis of celiac disease in pediatric age and a strict gluten free diet, lasting more than 12 months, allow celiac patients to reach a normal mineralization.

Objective: Conflicting evidence is reported about the effect of treatment on bone mineral density (BMD) in adults with celiac disease (CD). This study analyzed the effects on BMD induced by treatment with a calcium-rich, gluten-free diet in adults with nonsilent CD., Methods: In 30 women and 11 men with newly diagnosed CD, BMD was measured at the right femur (femoral neck and right Ward's triangle) and the lumbar spine by dual-energy x-ray absorptiometry under untreated conditions (pretreatment) and after 1-yr treatment with a calcium-rich, gluten-free diet., Results: On average, posttreatment BMD was greater than pretreatment BMD at the lumbar spine (mean +/- SE: 0.907 +/- 0.028 and 0.795 +/- 0.028 g/cm2, respectively; p < 0.001), the femoral neck (0.818 +/- 0.023 and 0.741 +/- 0.030 g/cm2, respectively; p = 0.002), and the Ward's triangle (0.703 +/- 0.025 and 0.654 +/- 0.025 g/cm2, respectively; p < 0.001). The greatest BMD change (percent of baseline) was observed at the lumbar spine (+14.1%), the smallest at the Ward's triangle (+7.5%). In the absence of appropriate controls, the BMD change expected in the patients under untreated conditions was estimated by regressing pretreatment BMD over duration of CD with control for gender and age at which CD became clinically evident. The regression coefficient of this analysis indicated that 1 yr of untreated CD was associated with a BMD decrease at the lumbar spine by 0.00570 g/cm2 (95% confidence interval -0.0103 to -0.0011 g/cm2). The 95% confidence interval of the treatment-induced change in BMD at the lumbar spine (+0.060 to +0.160 g/cm2) did not overlap the 95% confidence interval of the BMD change expected under untreated conditions. A large interindividual variability was observed in the BMD response to the treatment: in univariate and multivariate analyses, the treatment-induced change in BMD was significantly related to gender (greater in women than in men) and to pretreatment age and BMD., Conclusions: The data show that BMD is increased by dietary treatment of CD in most but not all adult patients; pretreatment BMD, gender, and pretreatment age predict the bone response after a 1-yr treatment.

Objectives: Low bone mineral density (BMD) has been demonstrated in some patients with chronic intestinal disorders accompanied by diarrhea and malabsorption. However, very few studies have evaluated BMD in patients with pancreatic insufficiency due to cystic fibrosis. Our aim was to assess the prevalence and severity of bone loss in a cohort of patients with pancreatic insufficiency as a consequence of chronic pancreatitis., Methods: Fourteen patients with chronic pancreatitis were studied. All of them presented with severe pancreatic insufficiency (secretin test: bicarbonate < or = 40 mEq/L) and steatorrhea (fecal fat > 7 g/day) and had been abstinent from alcohol for a median of 2.5 yr (range 1-15 yr). BMD was measured with a total-body scanner for dual-energy x-ray absorptiometry. Results were expressed as T-score (number of SD by which a patient density differs from the mean of sex-matched 30-yr-old healthy controls) in lumbar spine (L2-L4) and femoral neck. Total serum calcium, 25-(OH)D3, alkaline phosphatase, and midmolecular parathyroid hormone were determined., Results: Ten patients demonstrated osteopenia (T-score -1 to -2.5) in the lumbar spine and in the femoral neck. Three patients displayed osteoporosis (T-score < -2.5) in the lumbar spine and two in the femoral neck. Mean T-scores (+/- SEM) were -1.44 +/- 0.37 in the lumbar spine and -1.79 +/- 0.27 in the femoral neck. Total and ionic serum calcium, serum parathyroid hormone, and alkaline phosphatase were in the normal range in all patients. Serum 25-(OH)D3 was below normal range in 7 of 12 patients. T-scores of patients with pancreatitis of alcoholic etiology (n = 10) were similar to those of nonalcoholic patients (n = 4). BMD did not correlate with age, bicarbonate secretion, fecal fat excretion, stool volume, parameters of mineral metabolism, duration of alcoholism, or mean alcohol intake., Conclusions: Most patients with pancreatic insufficiency as a consequence of chronic pancreatitis exhibit osteopenia, and some show evidence of osteoporosis. Identifying the intimate mechanisms for low BMD are beyond the limitations of the present study. More in-depth metabolic studies are necessary to define the pathogenic mechanism of osteopenia associated with chronic pancreatic disorders.

Objectives: To determine the prevalence of hypovitaminosis D and secondary hyperparathyroidism (SHPT) and to assess bone turnover by using markers of bone formation and resorption in celiac disease (CD)., Methods: Forty-three patients with CD were investigated: group 1, newly diagnosed celiacs (n = 19); group 2, treated celiacs responding histologically to a gluten-free diet (n = 16); group 3, refractory celiacs, unresponsive to a gluten-free diet and immunosuppressive therapy (n = 8). Serum was drawn for intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], ionized calcium (Cai), total alkaline phosphatase (AP), and biochemical markers of bone formation: procollagen I carboxyterminal propeptide (PICP) and osteocalcin (Oc). Urinary indices of bone resorption, deoxypyridinoline (DPD), pyridinoline (PyD), and hydroxyproline (OHP), were measured in a 2-h fasting urine. In 22 patients, computerized tomographic scan for bone mineral density (BMD) was performed., Results: The prevalence in groups 1, 2, and 3, respectively, of hypovitaminosis D (< 50 nmol/L) was 58%, 25%, and 88%, and the prevalence of SHPT (> 5.4 pmol/L) was 25%, 19%, and 25%. Bone resorption markers were significantly elevated in all groups, and bone formation indices were elevated in the newly diagnosed celiacs compared with a group of healthy adults. Low BMD (T-score greater than -1 SD unit) was found in 68% of patients assessed; 36% of patients had a T-score greater than -2.5 SD units., Conclusions: Hypovitaminosis D and SHPT are common in newly diagnosed and refractory celiacs but are less common in those who respond to a gluten-free diet. Newly diagnosed patients have a high bone turnover state with elevation of both bone formation and resorption indices. Those with refractory disease demonstrate a remodeling imbalance with high bone resorption.

Background/aim: This is a study of patients with asymptomatic celiac disease. The aims of this study were: 1) To evaluate the nutritional status of asymptomatic patients with newly diagnosed celiac disease, and 2) to compare these findings with those of untreated/symptomatic and treated patients., Material: We examined 41 patients with celiac disease divided into three groups: a) 8 asymptomatic (diagnosed in a study of first-degree relatives of probands), b) 20 untreated/symptomatic patients, and c) 13 treated patients. Nutrition of patients from groups A and B was assessed at the time of diagnosis., Methods: Nutritional status was evaluated by: 1) body composition (fat and lean mass) by dual energy x-ray absorptiometry (DEXA), and 2) anthropometric measurements., Results: Compared with sex and age matched controls (n = 153), asymptomatic patients presented a moderate but significant reduction of the fat compartment (-29%; p < 0.001), but not of the lean-tissue mass (p = NS). Untreated/symptomatic patients showed a more severe depletion of fat (-46%; p < 0.001) and lean mass (-9.0%; p < 0.05) compared with healthy controls. Although fat mass of treated patients was significantly reduced with respect to controls (-24%; p < 0.003), lean mass was not affected. The anthropometric measurements of fat showed a significant correlation with the evaluation by DEXA (multiple regression analysis r = 0.918)., Conclusion: Asymptomatic patients in our study with an unequivocal diagnosis of celiac disease established by mucosal biopsy exhibited a modified body composition.

Objectives: Osteopenia is a well-known complication of overt celiac disease, but whether such defective bone mineralization is present among asymptomatic or silent patients is not known. Our objectives were: 1) to examine bone mineralization of a group of asymptomatic celiac patients; 2) to compare these results with those of symptomatic patients., Methods: Bone mineral density of the spine and total skeleton by dual energy x-ray absorptiometry and serum parameters of mineral metabolism of eight recently diagnosed asymptomatic patients with celiac disease were studied. Results were compared with those obtained in 20 untreated symptomatic celiacs, 14 patients treated with gluten-free diet for a mean time of 15 yr, and 153 healthy adult subjects, matched by sex and age., Results: Four and five out of eight asymptomatic patients presented with reduced mineralization of the spine and the total skeleton, respectively (> 1 SD below normal values for sex and age). Two patients presented with severe osteopenia of the spine, and the other three presented with severe osteopenia of the whole skeleton (> 2 SD below mean normal values). Osteopenia at plane bone level (total skeleton) was significantly lower when compared to healthy controls (p < 0.02). Symptomatic untreated patients had significantly more severe deterioration of bone mineralization than did asymptomatics (p < 0.05) and treated patients (p < 0.05). No difference in bone mineral density was observed between treated patients and asymptomatic celiacs. Serum levels of calcium, alkaline phosphatase, 25-OH vitamin D, and parathormone did not show conclusive abnormalities., Conclusions: Our findings provide direct evidence that reduced bone mineralization occurs in asymptomatic celiac patients before any other symptom becomes evident. Only early diagnosis and treatment of celiac disease can avoid the deterioration of the bone structure observed in all clinical status of celiac disease.

Celiac disease is the major nutrient-induced disease of the small intestine. The disease is traditionally characterized by villous atrophy responsive to gliadin. Recent data suggest that there is an extended spectrum of gluten sensitivity that includes first-degree relatives and patients with latent celiac disease. Genetic studies have identified HLA DQ A1 *0501 B1 *0201 as the predominant HLA gene most tightly linked to this condition. Gliadin-specific T cell clones restricted by DQ have now been identified in the small intestine lamina propria. Such T cells may be important in mediating many of the features of the disease. This review discusses the interrelationship of genetics, cereal chemistry, environmental factors, and immunology involved in the pathogenesis of celiac disease and explores its relationship with other nutrient-induced enteropathies.

Peripheral single photon absorptiometry was used to measure forearm bone mineral density in 22 celiacs on gluten-free diet from childhood (male 14, female 8, age 13-20) and 29 untreated adult celiacs at diagnosis (male 5, female 24, age 18-56, 14 with subclinical disease), compared with healthy sex- and age-matched controls. Bone mineral density was similar in patients treated from childhood and their controls [(668.4 +/- 65.3 vs. 654.9 +/- 69.6 mg/cm2, (mean +/- SD)], but significantly lower in untreated patients than in their controls (598.3 +/- 83.1 vs 673.2 +/- 42.7 mg/cm2, p less than 0.001). It was also significantly lower in the 12 younger untreated celiacs (18-28 yr) versus controls (619.4 +/- 68.5 vs 669.1 +/- 39.3 mg/cm2, p less than 0.01). In the untreated women, but not their controls, a negative correlation (p less than 0.05) was observed between bone mineral density and age. Bone mineral density did not correlate with severity of clinical or biochemical abnormalities. These results suggest that bone derangements are common in celiacs diagnosed in adulthood, even if they never presented evident malabsorption symptoms, and emphasize the importance of early diagnosis and treatment.

Intestinal permeability tests are a new class of tests of which the 51Cr-EDTA seemed the easiest to perform. We have evaluated the 8- and 24-h urinary excretion of ingested 51Cr-EDTA in 38 subjects. Twenty-seven patients with diseases not affecting the integrity of the small bowel served as controls. The test group consisted of two patients with celiac, six with Crohn's disease, and three with ulcerative colitis. Nineteen (70.37%) of the control patients had an abnormal test (more than 2.6% in 24 h). The patients with ulcerative colitis had normal excretion (mean 1.95% in 24 h). The patients with celiac disease had an elevated excretion (mean 3.62% in 24 h) and five out of six patients with Crohn's disease also had an increased excretion (mean 6.2% in 24 h). The elevated 51Cr-EDTA excretion in the control patients casts serious doubts on the validity of the test. Possible causes for abnormal excretion in the controls include various medications used by the patients as well as changes in the chromatographic mobility of 51Cr-EDTA, demonstrated by us after incubation with gastric juice.

A patient with celiac disease and mesenteric adenopathy discovered on computerized scanning of the abdomen is described. Lymphadenopathy resolved more than 6 months after the institution of a gluten-free diet. Adenopathy without evidence of lymphoma may be part of the clinical manifestations of patients with celiac disease. Follow-up with computerized tomography may be an option in patients with low clinical suspicion for lymphoma.

Forty-three patients suffering from familial amyloidosis with polyneuropathy were examined by means of barium meal, barium follow through, barium enema, cholecystogram, and gastroscopy. The findings were reviewed with respect to the presence of steatorrhea and impaired d-xylose absorption. Seven patients had gastric stasis (without gross anatomical changes) on barium meal examination and seven others on the gastroscopy. Gastroscopy revealed that another five patients had inactive peristalsis of the antrum-pylorus. Only one patient had slow transit of barium on follow through. The transit time of barium did not correlate with increased fecal fat output or decreased d-xylose absorption. Barium enema and cholecystogram were normal. The main radiological and gastroscopic finding in familial amyloidosis with polyneuropathy was reduced gastric motility.