Osteogenesis imperfecta (OI) is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI = 45.4) and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD) with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD), having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD.

A 3-year-old girl presented with a hemorrhagic conjunctival lesion in the right eye. The medical history revealed premature cessation of breast feeding, intolerance to the ingestion of baby foods, anorexia, and abdominal distention. Prior to her referral, endoscopic small intestinal biopsy had been carried out under general anesthesia with a possible diagnosis of Celiac Disease (CD). Her parents did not want their child to undergo general anesthesia for the second time for the excisional biopsy. We decided to follow the patient until all systemic investigations were concluded. In evaluation, the case was diagnosed with CD and the conjunctival tumor showed complete regression during gluten-free dietary treatment. The clinical fleshy appearance of the lesion with spider-like vascular extensions and subconjunctival hemorrhagic spots, possible association with an acquired immune system dysfunction due to CD, and spontaneous regression by a gluten-free diet led us to make a presumed diagnosis of conjunctival Kaposi sarcoma.

Adult celiac disease (CD) presents with very diverse symptoms that are clearly different from those typically seen in pediatric patients, including ferropenic anemia, dyspepsia, endocrine alterations and elevated transaminase concentration. We present the case of a 51-year-old overweight woman with altered basal blood glucose, hypercholesterolemia, hypertriglyceridemia and persisting elevated transaminase levels, who showed all the symptoms for a diagnosis of metabolic syndrome. Because she presented iron deficiency anemia, she was referred to the gastroenterology department and subsequently diagnosed with celiac disease after duodenal biopsies and detection of a compatible HLA haplotype. Gluten-free diet (GFD) was prescribed and after 6 mo the patient showed resolution of laboratory abnormalities (including recovering anemia and iron reserves, normalization of altered lipid and liver function parameters and decrease of glucose blood levels). No changes in weight or waist circumference were observed and no significant changes in diet were documented apart from the GFD. The present case study is the first reported description of an association between CD and metabolic syndrome, and invites investigation of the metabolic changes induced by gluten in celiac patients.

BACKGROUND: Coeliac disease is managed by life-long gluten withdrawal from the diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Novel therapeutic approaches are needed to supplement or even replace the dietary treatment. AIM: To review recent advances in new therapeutic options for coeliac disease.

METHODS: A literature search was performed on MEDLINE, EMBASE, Web of Science, Scopus, DDW.org and ClinicalTrials.gov for English articles and abstracts. The search terms used included, but not limited to, 'Celiac disease', 'new', 'novel', 'Advances', 'alternatives' and 'Drug therapy'. The cited articles were selected based on the relevancy to the review objective.

RESULTS: Several new therapeutic approaches for coeliac disease are currently under development by targeting its underlying pathogenesis. Alternative therapies range from reproduction of harmless wheat strains to immunomodulatory approaches. Some of these therapies such as enzymatic cleavage of gluten and permeability inhibitors have shown promise in clinical studies.

CONCLUSIONS: Gluten-free diet is still the only practical treatment for patients with coeliac disease. Novel strategies provide promise of alternative adjunctive approaches to diet restriction alone for patients with this disorder.

A tremendous amount of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with non-alcoholic steatohepatitis, the additive role of vitamins B12 and D to the standard therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the positive outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychologically accepted by patients as a natural compound with relative safety and low cost, their use should be encouraged in the fields where positive data are available.

A 33-year-old patient, with pre-existing diagnosis of 'schizophrenic' disorder, came to our observation for severe diarrhoea and weight loss. Use of single photon emission computed tomography, (99mTc)HMPAO SPECT, demonstrated hypoperfusion of the left frontal brain area, without evidence of structural cerebral abnormalities. Jejunal biopsy showed villous atrophy. Antiendomysial antibodies were present. A gluten-free diet was started, resulting in a disappearence of psychiatric symptoms, and normalization of histological duodenal findings and of (99mTc)HMPAO SPECT pattern. This is the first case in which, in an undiagnosed and untreated coeliac patient with psychiatric manifestations, the (99mTc)HMPAO SPECT demonstrated a dysfunction of frontal cortex disappearing after a gluten-free diet.

BACKGROUND:A non-negligible percentage of patients with non-alcoholic fatty liver disease, a leading cause of hepatic progressive disorder related to insulin resistance, have no metabolic risk factors, and abnormal intestinal permeability has been suggested to be involved in the pathogenesis of the liver damage. Coeliac disease, a curable disorder characterised by inflammatory mucosal damage, may show hepatic histological features similar to steatohepatitis. Conflicting data have been reported on the prevalence of coeliac disease in non-alcoholic steatohepatitis.

AIM:To search for coeliac disease in a series of patients with non-alcoholic fatty liver disease by screening with anti-tissue transglutaminase and anti-endomysium antibodies.

PATIENTS AND METHODS:Fifty-nine consecutive patients with hypertransaminasemia and non-alcoholic fatty liver disease, 38 (64%) with steatohepatitis. Anti-endomysium antibodies were assayed by indirect immunofluorescence, IgA anti-tissue transglutaminase by ELISA. Patients who tested positive underwent HLA DQ typing and endoscopy.

RESULTS:Tissue transglutaminase antibodies were positive in six (10%) patients and anti-endomysium in two (3.4%); only two (3.4%), positive for both anti-endomysium positive and anti-transglutaminase, resulted to have coeliac disease based on histological findings. After 6 months of gluten-free diet, liver enzymes normalised.

CONCLUSIONS:The prevalence of silent coeliac disease is 3.4% in patients with non-alcoholic fatty liver. The inclusion of anti-endomysium antibodies test in studying patients with non-alcoholic fatty liver and persistent biochemical abnormalities has to be taken into account, since positivity for tissue transglutaminase antibodies, in the absence of confirmatory anti-endomysium antibodies, is not sufficient to perform diagnostic endoscopy.

OBJECTIVE:Leptin has effects on growth and is also involved in immune regulation. We thought that with its intestinal histopathologic alterations due to immune mechanisms, and subsequent malnutrition and/or growth failure, celiac disease (CD) deserves interest regarding leptin status.

METHOD:Serum leptin levels of 19 children with CD on admission and 1 year after gluten-free diet (GFD) and of 16 healthy children were determined.

RESULTS:Mean age was 9.7+/-3.3 years. Mean serum leptin level of children with CD on admission and of healthy children were 1.60+/-0.63 ng/mL, and 3.98+/-1.49 ng/mL, respectively (P: 0.0001). Mean serum leptin level under GFD was 4.55+/-1.97 ng/mL. There was a statistical significant difference between serum levels determined before and 1 year after GFD (P: 0.001) and between those of under GFD and healthy children (P: 0.001). Of 19 patients with CD, 10 (52.6%) showed Marsh IIIc, other 9 (47.4%) showed Marsh IIIa histologic lesions. Mean serum leptin level of children with Marsh IIIc and Marsh IIIa were not different (1.70+/-0.73 ng/mL vs. 1.45+/-0.59 ng/mL). Leptin was correlated with body mass index in healthy children, and in CD both before and after GFD (P<0.001). Mean lumbar z score of the patients on admission and after GFD were 2.7+/-1.3 and 1.9+/-0.8, respectively (P: 0.048). Serum leptin level was not correlated with lumbar z score either before or after GFD.

CONCLUSIONS:Serum leptin level is affected in childhood CD, it is not directly related to histopathologic findings, and is responsive to GFD. Further studies investigating its level in different clinical and histopathologic presentations might give clear clues about the role of leptin in CD.

OBJECTIVES:To assess the usefulness of a new class of antibodies, the anti-deamidated gliadin peptides, in the diagnostic approach to children less than 2 years with suspected celiac disease.

PATIENTS AND METHODS:We investigated 40 children (median age: 16.8 months; age range: 4-24 months), with symptoms and signs of chronic enteropathy and high serum levels of conventional anti-gliadin antibodies, but normal values of anti-transglutaminase and anti-endomysial antibodies; all underwent measurement of anti-deamidated gliadin peptides serum levels, upper gastrointestinal endoscopy with biopsies and HLA typing; 40 subjects served as controls.

RESULTS:In 29 patients (group A) serum levels of anti-deamidated gliadin peptides were normal and duodenal histology showed a spectrum of abnormalities ranging from mucosal inflammatory infiltrates to villous damage (in almost all cases compatible with Marsh 1-to-2 lesions). All improved on a cow's and soy milk free diet containing gluten. In 11 patients (group B) there were high serum levels of anti-deamidated gliadin peptides and histology showed features suggestive of celiac disease (Marsh 2-to-3 lesions) in all; furthermore, human leucocyte antigen typing was consistent with a celiac disease genetic pattern in all. Group B patients significantly improved on a gluten free diet containing cow's and soy milk proteins. None of the control group was anti-deamidated gliadin peptides positive.

CONCLUSIONS:In children younger than 2 years with signs of chronic enteropathy and normal values of classical serum markers of celiac disease, the latter can be predicted by high serum levels of anti-deamidated gliadin peptides.

In most developed countries, gluten is currently most commonly introduced between 4 and 6 months of age, in spite of little evidence to support this practice. As for infants at risk of developing food allergies, there is clear evidence that introducing solid foods before the end of the 3rd month is detrimental and should be avoided. A recent growing body of evidence however challenges the notion that solids (and among them, gluten-containing foods) should be introduced beyond the 6th month of life. Another important aspect of gluten introduction into the diet has to do with its possible role in causing type-1 diabetes (IDDM). Recently, a large epidemiological investigation in a cohort of children at risk for IDDM found that exposure to cereals (rice, wheat, oats, barley, rye) that occurred early (< or = 3 months) as well as late (> or = 7 months) resulted in a significantly higher risk of the appearance of islet cell autoimmunity compared to the introduction between 4 and 6 months. As for celiac disease, the protective role of breastfeeding can be considered ascertained, especially the protection offered by having gluten introduced while breastfeeding is continued. Evidence is emerging that early (< or = 3 months) and perhaps even late (7 months or after) first exposure to gluten may favor the onset of celiac disease in predisposed individuals. Additionally, large amounts of gluten at weaning are associated with an increased risk of developing celiac disease, as documented in studies from Scandinavian countries. In celiac children observed in our center, we could show that breastfeeding at the time of gluten introduction delays the appearance of celiac disease and makes it less likely that its presentation is predominantly gastrointestinal. Based on current evidence, it appears reasonable to recommend that gluten be introduced in small amounts in the diet between 4 and 6 months, while the infant is breastfed, and that breastfeeding is continued for at least a further 2-3 months.

Abstract Background. Liver involvement in celiac disease (CD) is clinically relevant and could require specific treatment in addition to gluten-free diet (GFD). Transient elastography (TE), a noninvasive tool for assessing liver stiffness (LS), has widely been reported as an accurate surrogate marker of liver fibrosis. Aims. To prospectively identify celiac patients with liver involvement by TE and to assess the effect of GFD. Material and methods. Ninety-five histologically confirmed CD patients (24 newly diagnosed) were consecutively evaluated by TE and compared with 146 patients with chronic hepatitis C (HCV) and 54 healthy subjects. Results. LS ranged between 2.8 and 6.7 kPa (median 4.9) in healthy subjects, defining 6.9 kPa as the upper reference limit (2 SD above the mean levels). TE was above 6.9 kPa in 10 (10.5%) CD patients. Median TE values resulted significantly higher in CD patients with hypertransaminasemia than those without [6.1 vs. 4.2 kPa (p<0.01)]. Among the 24 newly diagnosed patients with CD, median TE values declined from 4.4 to 4 kPa, after 6 months of GFD, resulting below 6.9 kPa in 100% of the patients. Conclusions. A subset of CD patients with hypertransaminasemia showed liver involvement by TE. Accordingly, based on its accuracy in predicting liver fibrosis, TE could be used to identify those CD patients suitable for liver biopsy.

Paroxysmal visual manifestations may represent epileptic seizures arising from the occipital lobe. In coeliac disease (CD) bilateral occipital calcifications and seizure semiology consistent with an occipital origin have been described, primarily in Mediterranean countries. By reporting three adult patients from an Australian outpatient clinic with visual disturbances, occipital cerebral calcifications, and CD, this study seeks to emphasise that CD should be considered even when patients of non-Mediterranean origin present with these symptoms. Seizure types included simple partial, complex-partial, and secondarily generalised seizures. The seizure semiology consisted of visual disturbances such as: blurred vision, loss of focus, seeing coloured dots, and brief stereotyped complex visual hallucinations like seeing unfamiliar faces or scenes. Symptoms of malabsorption were not always present. Neurological examination was unremarkable in two patients, impaired dexterity and mild hemiatrophy on the left was noted in one. Routine electroencephalography was unremarkable. In all cases, computed tomography demonstrated bilateral cortical calcification of the occipital-parietal regions. Magnetic resonance imaging showed no additional lesion. All patients had biopsy confirmed CD. Seizure control improved after treatment with gluten free diet and anticonvulsants. This report illustrates the association between seizures of occipital origin, cerebral calcifications, and CD even in patients not of Mediterranean origin.

ObjectiveTo update the evidence published in a previous systematic review and meta-analysis that compared the effect of breastfeeding on risk of coeliac disease (CD).Material and methodsA systematic review of observational studies published between 1966 and May 2004 on the subject was conducted in 2005. This update is a systematic review of observational studies published between June 2004 and April 2011. Pubmed, EMBASE and Cinahl were searched for published studies that examined the association between breastfeeding and CD.ResultsAfter duplicates were removed 90 citations were screened. Four observational studies were included in the review. Two of three studies which had examined the duration of breastfeeding and CD reported significant associations between longer duration of breastfeeding and later onset of CD (OR ranged from 0.18 to 0.665). Breastfeeding during the introduction of gluten to the infant was reported to have a protective effect in two studies.ConclusionsOur findings support previous published findings that breastfeeding seems to offer a protection against the development of CD in predisposed infants. Breastfeeding at time of gluten introduction is the most significant variable in reducing the risk. Timing of gluten introduction may also be a factor in the development of CD.