Pubblicazioni scientifiche

Una breve raccolta di articoli scientifici sulla celiachia per comprendere meglio gli aspetti clinici e psicosociali.


Celiac Disease in Infants: Prevention and Dietary Treatment

Nutrition and Health 2013, pp 145-151

Mukadder Ayşe Selimoğlu

Celiac disease (CD) is the most common malabsorption in the world, and is a major healthcare issue. It is an immune-mediated gluten-dependent enteropathy, which has a wide range of clinical manifestations and variable severity. It is triggered by the ingestion of gluten, which is found in wheat, rye, and barley, in genetically susceptible individuals. While typical clinical manifestations of CD include failure to thrive, chronic diarrhea, and anemia, a significant proportion of patients present with atypical symptoms, such as skin lesions, isolated hypertransaminasemia, dental or neurological problems [1–3]. A changing pattern in the presentation of pediatric CD, such as a more frequent diagnosis in older children, mostly presents with atypical symptoms, is reported [4]. Typical (classical) CD is more common in younger children (mainly between 6 and 18 months of age) and frequently is associated with more severe intestinal injury [5].


Down Syndrome Is Associated with Elevated Risk of Celiac Disease: A Nationwide Case-Control Study

The Journal of Pediatrics – February 2013

Karl Mårild, Olof Stephansson, Lena Grahnquist, Sven Cnattingius, Gabriella Söderman, Jonas F. Ludvigsson

To provide risk estimates for celiac disease (CD) in Down syndrome (DS) compared with the general population.

Study design
In this nationwide Swedish case-control study, we examined the risk of CD in individuals with DS born between 1973 and 2008. Study participants consisted of 2 populations: 11 749 patients with biopsy-verified CD (villous atrophy [VA], equivalent to Marsh grade III) who were identified through histopathology reports from the 28 pathology departments in Sweden and 53 887 population-based controls matched for sex, age, calendar year of birth, and county of residence. We used prospectively recorded data from Swedish health registers to identify individuals with DS. ORs were calculated using conditional logistic regression.

Of the 11 749 individuals with CD, 165 had a diagnosis of DS (1.4%) compared with 55/53 887 controls (0.1%). This corresponded to an OR of 6.15 (95% CI = 5.09-7.43) for subsequent CD in individuals with DS compared with the general population. The association between DS and CD was not affected by maternal age at delivery, infant sex, or presence of type 1 diabetes mellitus in the child.

We found a sixfold increased risk of CD in individuals with DS. This study adds precision to the previously reported association between DS and CD.



Biomarkers for Diagnosis and Monitoring of Celiac Disease

Journal of Clinical Gastroenterology: 5 February 2013

Vives-Pi, Marta PhD; Takasawa, Shin PhD; Pujol-Autonell, Irma BSc; Planas, Raquel PhD; Cabre, Eduard PhD; Ojanguren, Isabel PhD; Montraveta, Montserrat MD; Santos, Agustin L. BSc; Ruiz-Ortiz, Estíbaliz BSc

Celiac disease (CD) is an autoimmune disorder, which damages the small intestine and is caused by ingestion of gluten in genetically susceptible individuals. The only known effective treatment is a lifelong gluten-free diet. Genetic risk factors have been identified and nearly all patients are HLA-DQ2 and/or HLA-DQ8 positive. Specific autoantibodies, IgA antitissue transglutaminase-2, antiendomysium, and antideaminated forms of gliadin peptide antibodies, are widely used as diagnostic aids in celiac patients. However, the discovery of new biomarkers may help in the diagnosis and follow-up of the disease. Recently, the molecule REG I[alpha], involved in tissue regeneration, has been proposed as a new biomarker of CD. REG I[alpha] expression is increased in the target tissue and in the sera of celiac patients during damage and inflammation, decreasing after gluten-free diet. In this article we review the main biomarkers for diagnosis and monitoring of CD, focusing on the immune response-related mechanisms.


Hepatitis B vaccine in celiac disease: Yesterday, today and tomorrow

World J Gastroenterol. 2013 February 14; 19(6): 838-845.

Giovanna Vitaliti, Andrea Domenico Praticò, Carla Cimino, Giovanna Di Dio, Elena Lionetti, Mario La Rosa and Salvatore Leonardi.

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.


Prior Endoscopy in Patients with Newly Diagnosed Celiac Disease: A Missed Opportunity?

Dig Dis Sci. 2013 Jan 30

Lebwohl B, Bhagat G, Markoff S, Lewis SK, Smukalla S, Neugut AI, Green PH.

Celiac disease (CD) is under-diagnosed in the United States, and factors related to the performance of endoscopy may be contributory.
To identify newly diagnosed patients with CD who had undergone a prior esophagogastroduodenoscopy (EGD) and examine factors contributing to the missed diagnosis.
We identified all patients age ≥18 years whose diagnosis of CD was made by endoscopy with biopsy at our institution (n = 316), and searched the medical record for a prior EGD. We compared those patients with a prior EGD to those with without a prior EGD with regard to age at diagnosis and gender, and enumerated the indications for EGD.
Of the 316 patients diagnosed by EGD with biopsy at our center, 17 (5 %) had previously undergone EGD. During the prior non-diagnostic EGD, a duodenal biopsy was not performed in 59 % of the patients, and ≥4 specimens (the recommended number) were submitted in only 29 % of the patients. On the diagnostic EGD, ≥4 specimens were submitted in 94 %. The mean age of diagnosis of those with missed/incident CD was 53.1 years, slightly older than those diagnosed with CD on their first EGD (46.8 years, p = 0.11). Both groups were predominantly female (missed/incident CD: 65 vs. 66 %, p = 0.94).
Among 17 CD patients who had previously undergone a non-diagnostic EGD, non-performance of duodenal biopsy during the prior EGD was the dominant feature. Routine performance of duodenal biopsy during EGD for the indications of dyspepsia and reflux may improve CD diagnosis rates.


Gastrointestinal and Non-gastrointestinal Presentation in Patients with Celiac Disease

Arch Iran Med. 2013 Feb;16(2):78-82. doi: 013162/AIM.006.

Ehsani-Ardakani MJ, Rostami Nejad M, Villanacci V, Volta U, Manenti S, Caio G, Giovenali P, Becheanu G, Diculescu M, Pellegrino S, Magazzù G, Casella G, Di Bella C, Decarli N, Biancalani M, Bassotti G, Hogg-Kollars S, Zali MR, Rostami K.

Celiac disease (CD) may have a variety of different presentations. This study has aimed to explore the prevalence of gastrointestinal (GI) and non-GI symptoms in patients with CD according to data collected in Italy and Romania (Europe) and Iran (Middle East).
This is a retrospective cross-sectional study conducted in Iran, Romania and Italy with data collection during the period from May 2009 – May 2011. For each center we included only patients with CD that was confirmed by endoscopy, small bowel biopsies and positive serology. GI symptoms such as abdominal pain, diarrhea, constipation, nausea and vomiting, weight loss and flatulence, as well as additional signs and symptoms of iron deficiency anemia (IDA), osteoporosis, hypertransaminasemia, and other related abnormalities were collected.
Overall, 323 women and 127 men, whose mean age at diagnosis was 34.2 ± 16.47 years were included in this study. Of these, 157 subjects (34.9%) reported at least one GI symptom. The majority of cases had the following primary presenting GI symptoms: diarrhea (13.6%), dyspepsia and constipation (4.0%). Other disease symptoms were reported by 168 (37.3%) patients. The most presenting non-GI symptoms in the majority of cases were anemia (20.7%) and osteopenia (6%). There were statistically significant differences between the majority of symptoms when we compared the reported clinical symptoms from different countries.
This study indicated that upper abdominal disorders such as abdominal pain and dyspepsia were the most common primary complaints among European patients, whereas Iranian patients had complaints of diarrhea and bloating as the classic presentations of CD. For non-GI symptoms, anemia was the most frequent complaint for both Iranian and Italian patients; however it was significantly higher in Iranians.


Testing for Anti-reticulin Antibodies in Celiac Disease is Obsolete: A Review of Recommendations for Serologic Screening and the Literature

Clin. Vaccine Immunol. 30 January 2013,

Sarada L. Nandiwada, Anne E. Tebo

Celiac disease (CD) is an autoimmune disorder that occurs in genetically susceptible individuals of all ages and is triggered by immune response to gluten and related proteins. The disease is characterized by the presence of HLA-DQ2 and/or DQ8 haplotypes, diverse clinical manifestations, gluten-sensitive enteropathy and production of several autoantibodies of which endomysial, tissue transglutaminase and deamidated gliadin peptide antibodies are considered specific. Although anti-reticulin antibodies (ARA) have historically been used in the evaluation of CD, these assays lack optimal sensitivities and specificities for routine diagnostic use. This review highlights the advances in CD-specific serologic testing and the rationale for eliminating ARA from CD evaluation consistent with recommendations for diagnosis.


Ménière disease and gluten sensitivity: Recovery after a gluten-free diet

American Journal of Otolaryngology – Available online 30 January 2013

Federica Di Berardino, Eliana Filipponi, Dario Alpini, Tom O’Bryan, Daniela Soi, Antonio Cesarani

We report the case of a 63-year-old female with definite unilateral Ménière disease, osteoarthritis of the distal finger joints with mucous cysts and Heberden’s nodes, and constipation with recurrent abdominal pain whose symptoms remitted after 6 months of a restrictive gluten-free diet.

1. Introduction
Gluten-related disorders have been known for many years and are an example of an auto-immune disease caused by polymorphism of the immune response. Gluten is the trigger of three heterogeneous sets of conditions: 1) immune-mediated enteropathy (celiac disease), 2) wheat allergy, 3) non-celiac gluten sensitivity. These three distinct diseases can induce many different and specific manifestations, mediated by innate and adaptive immune pathways which are not common to all three conditions. Inhalant and food allergies have been linked with Ménière disease (MD) symptoms and and recently a relation between gluten sensitivity (GS) and MD symptoms has been proposed.

2. Case-report
We describe the case of a 63-year-old female affected from January 2007 by definite unilateral (right ear) MD according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Aequilibrium (AAO-HNS CHE) criteria: she had a history of three definitive spontaneous episodes of vertigo lasting 20 min or longer, with audiometrically documented sensorineural hearing loss of at least 60 dB HL on one occasion, tinnitus and aural fullness. A right peripheral vestibular lesion was detected upon bithermal caloric test according to the Hallpike technique using Jongkees’ formula.
The patient also suffered from osteoarthritis of the distal finger joints with mucous cysts, Heberden’s nodes and constipation with recurrent abdominal pain.
Skin prick tests were positive to gliadin after 12 h and were negative to the most common inhalants and food (cow milk proteins, ovoalbumin, water extract from wheat flour; tomato, potato, apple, and carrot [fresh foods]). Both specific IgE tests for common allergens and wheat, and screening for celiac disease were negative. Upper gastrointestinal endoscopy and duodenal biopsy were also negative (Marsh 0). In 2006, the patient had already undergone a total colonoscopy for constipation, recurrent abdominal pain and hemorrhoids with negative results.
A possible role of the hypersensitivity to gliadin was hypothesized and the patient agreed to follow a restrictive gluten-free diet, eliminating foods that contain wheat, rye, barley, oats, farro, kamut and their derivatives. After six months, remission from all symptoms was complete and the benefit still persists. In particular, the progression of the arthritis has been arrested as has the formation of mucous cysts and Heberden’s nodules. The subject has had no further episodes of vertigo and the pure-tone threshold has remained unchanged. She also reported that she was no longer suffering from constipation. This optimal condition still persists after almost five years provided the gluten-free diet is respected. Taking into account avoidance of cross-contamination and quantity and frequency of gluten exposure, the gluten-free diet adherence was excellent.
There was only one casual intake of dietary gluten, which caused a rapid relapse of the hand osteoarthritis after only one day. Having followed the gluten-free diet for almost 5 years, the patient decided to try reintroducing gluten into her diet but, one week later, she had a severe episode of vertigo with aural fullness, slight worsening of hearing loss at low frequencies, reappearance of tinnitus and worsening of hand osteoarthritis.

3. Discussion
GS has been defined by the presence of morphological, functional and immunological disorders that respond to gluten exclusion and yet lack the characteristic features that define celiac disease and wheat allergy.
Arthritic symptoms with mucous cysts, small erosions of the interphalangeal joints and Heberden’s nodes have been associated with gluten-related disorders with improvement on a gluten-free diet. Constipation has been identified in 18% of non-celiac gluten sensitive patients. Numerous mechanisms have been postulated in the development of altered motility from gluten-related disorders. Consistent data are available on the presence of disturbed gastrointestinal motility of untreated patients with a gluten-related disorder and the fact that this condition reverses on a gluten-free diet.
In our MD patient, a gluten-free diet arrested the progression of the arthritis, the formation of mucous cysts and Heberden’s nodules, with complete remission of vertigo and aural symptoms. The remission was still evident after more than four and a half years of follow-up. The effect of casual or intentional gluten intake suggests a possible cause/effect correlation.

4. Conclusion
To the best of our knowledge, this is the only documented case of recovery from non-celiac, non-allergic gluten sensitivity symptoms after a gluten-free diet in an MD subject.
Further investigation is needed to confirm the hypothesis that there is an association between gluten and MD symptoms.


Patients with Celiac Disease Have a Lower Prevalence of Non-Insulin Dependent Diabetes Mellitus and Metabolic Syndrome

Gastroenterology. 2013 Jan 24

Kabbani TA, Kelly CP, Betensky RA, Hansen J, Pallav K, Villafuerte J, Vanga RR, Mukherjee R, Novero A, Dennis M, Leffler DA.

We investigated whether risk for non-insulin dependent diabetes mellitus (NIDDM) and metabolic syndrome are affected by celiac disease. We examined the prevalence of NIDDM and metabolic syndrome among adults with celiac disease, compared with matched controls.
We assessed medical records of 840 patients with biopsy-proven celiac disease for diagnoses of NIDDM, hypertension, or hyperlipidemia; body mass index (BMI); lipid profile; and levels of glucose or glycosylated hemoglobin, to identify those with metabolic syndrome. Patients without celiac disease were matched for age, sex, and ethnicity (n=840, controls). The prevalence of NIDDM and metabolic syndrome in the celiac disease cohort was compared with that of the controls and subjects included in the National Health and Nutrition Examination Survey (NHANES).
Twenty-six patients with celiac disease (3.1%) had NIDDM compared to 81 controls (9.6%) (P <.0001). Similarly, the prevalence of metabolic syndrome was significantly lower among patients with celiac disease than controls (3.5% vs. 12.7%; P <.0001). The mean BMI of patients with celiac disease was significantly lower than that of controls (24.7 vs. 27.5; P <.0001). However, celiac disease was still associated with a lower risk of NIDDM, after controlling for BMI. Furthermore, the prevalence of NIDDM in the celiac group was significantly lower than the NHANES population, in all BMI categories.
The prevalence of NIDDM and metabolic syndrome are lower among patients with celiac disease than in matched controls and the general population. These differences are not explained by differences in BMI. Studies are needed to determine the mechanisms by which celiac disease affects the risk for NIDDM and metabolic syndrome.


Children With Celiac Disease: Effect of Gluten-Free Diet on Growth and Body Composition

Topics in Clinical Nutrition: January/March 2013 – Volume 28 – Issue 1 – p 93–98

Lily, Hong MPH, RD

Celiac disease is an autoimmune disorder characterized by immunologically mediated intolerance to gluten, the only medical intervention is lifelong gluten withdrawal or avoidance. Celiac disease is a common disorder among children. Early diagnosis and diet therapy are crucial, as children experience high growth velocity in this phase of their life. This article reviews recent literature on the impact of celiac disease on growth and body composition on children and describes the outcome following a gluten-free diet.


Vitamin D Status and Concomitant Autoimmunity in Celiac Disease

Journal of Clinical Gastroenterology: January 2013

Tavakkoli, Anna MD; DiGiacomo, Daniel MS; Green, Peter H. MD; Lebwohl, Benjamin MD, MS

Goals: To determine whether patients with celiac disease (CD) and low vitamin D levels also have a higher prevalence of other autoimmune diseases (AD) as compared with patients with normal vitamin D levels.
Background: Patients with CD carry a higher risk of other autoimmune disorders. Because of its immunoregulatory properties, vitamin D deficiency has been proposed in the pathogenesis of a variety of AD. Whether low vitamin D levels in patients with CD can predict concomitant AD is unknown.
Study: A retrospective cross-sectional study of 530 adult patients with CD and a 25-hydroxyvitamin D level on record at Columbia University Medical Center.
Results: One hundred thirty-three patients (25%) had vitamin D deficiency. The prevalence of AD was similar among those with normal vitamin D levels (11%), insufficiency (9%), and deficiency (12%, P=0.66). On multivariate analysis, adjusting for age of CD diagnosis and sex, vitamin D deficiency was not associated with AD (odds ratio, 1.35; 95% confidence interval, 0.62-2.95). The risk of psoriasis was higher in patients with vitamin D deficiency (7% vs. 3%, P=0.04). Vitamin D deficiency was more common in those who presented with anemia (39%) than in those who did not (23% P=0.002).
Conclusions: Vitamin D deficiency in CD is common but does not predict AD. The risk of psoriasis is increased in vitamin D-deficient CD patients. Assessment of vitamin D seems to be a high-yield practice, especially in those CD patients who present with anemia.


Celiac disease in a child with ulcerative colitis: a possible genetic association

J Clin Gastroenterol. 2013 Feb;47(2):127-9.

Cheng SX, Raizner A, Phatak UP, Cho JH, Pashankar DS.

Celiac disease and inflammatory bowel disease including ulcerative colitis (UC) and Crohn’s disease are both immune-mediated enteropathies. It is rare for both celiac disease and inflammatory bowel disease to occur together in an individual patient. This association has been reported in adults, however, very rarely in children. Here, we report an unusual case of an 8-year-old child with a history of anemia and failure to thrive who presented with bloody diarrhea. His evaluation showed anemia, elevated inflammatory markers, and positive celiac antibodies. Endoscopic evaluation revealed partial duodenal villous atrophy and pancolitis. He was diagnosed with celiac disease and UC and responded well to a gluten-free diet and steroid/mesalamine therapy. The patient’s genetic testing revealed markers showing susceptibility for both celiac disease and UC. It is important to be aware of this association as both conditions can present with similar clinical features, however, require different therapeutic approaches.


World gastroenterology organisation global guidelines on celiac disease

J Clin Gastroenterol. 2013 Feb;47(2):121-6.

Bai JC, Fried M, Corazza GR, Schuppan D, Farthing M, Catassi C, Greco L, Cohen H, Ciacci C, Eliakim R, Fasano A, González A, Krabshuis JH, LeMair A.


A Case of Multiple Sclerosis and Celiac Disease

Case Reports in Neurological Medicine, Volume 2013

H. Z. Batur-Caglayan, C. Irkec, I. Yildirim-Capraz, N. Atalay-Akyurek, and S. Dumlu Uniersity,

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS). Since a correlation between gluten intake and incidence of MS had been reported, the relationship of antigliadin antibodies and MS was debated.
Case Report. We report the case of a 45-year-old female MS patient who is under interferon treatment. After seven years of monitoring, during her routine gastroenterological assessment, she was diagnosed with celiac disease.
Conclusion. Beside the neurological manifestations that have been demonstrated in about 10% of celiac disease (CD) patients, white-matter abnormalities in brain MRI are uncommon and controversial. But in the literature, MS seems to be associated with CD as in our patient. We suggest that MS patients with gastroenterological complaints should undergo an assessment for CD.

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS). MS, resembling other autoimmune disorders, has a multifactorial etiology, including environmental, immunological, and genetic factors. MS is sometimes difficult to be differentiated from CNS involvement in systemic autoimmune diseases [1].Celiac disease is an immune-mediated intestinal disorder with gluten sensitivity which is characterized with villous atrophy and crypt hyperplasia. Celiac disease is well known to be associated with many neurological diseases like cerebellar ataxia, peripheral neuropathy, epilepsy, dementia, and depression. Earlier reports mainly have documented the involvement of the nervous system as a complication of prediagnosed CD. As gluten sensitivity with or without intestinal involvement shows concurrence with neurological manifestations like white-matter lesions, MS has been studied for the association with gluten sensitivity [2–5]. We describe an MS patient who is diagnosed with CD after seven years of followup.

Case Report
Seven years ago, at the age of 38, a female patient was consulted to our clinic with right leg weakness and paresthesias in her arms and legs. Neurological examination showed right hemiparesis (4/5) and right hemihypoesthesia. Past history was unremarkable except that she had irritable bowel syndrome and iron deficiency anaemia. Routine laboratory investigations revealed haemoglobin of 12,4 g/dL with MCV of 80,8 and serum ferritin 6,36 ng/mL (normal values 7–270 ng/mL) confirming a mild iron deficiency. Detailed biochemical and immunological profiles were normal. Vitamin B12, folate, ANA, anti-dsDNA antibodies, ANCA, ASMA, AMA, and anticardiolipin and antiphospholipid antibodies were normal. Brain MRI showed T1 isointense and T2 hyperintense abnormalities in deep periventricular white matter and left ventricular trigone (Figure 1(a)). Cervical spine MRI showed an expanding focal lesion at level C2 with gadolinium enhancement (Figure 1(b)). Cerebrospinal fluid investigation represents mildly increased IgG index but not with oligoclonal bands. Visual-, somatosensory-, and motor-evoked potentials assessments were normal. The patient was treated with intravenous methylprednisolone for 5 days. Motor and sensory symptoms gradually improved. After one year, she was readmitted to a local hospital in another city three times with symptoms like right hemiparesis, visual blurring in right eye, dizziness, and diplopia. She had received methyl prednisolone for ten days. Repeated brain MRI showed millimetric signal changes in periventricular region. According to Mc Donald’s criteria, MS diagnosis had been made. Because of the relapsing course of disease, the presence of paresthesias, Uhthoff’s phenomenon, and Lhermitte’s sign, beta interferon therapy was planned. In a seven-year observation, two attacks as paraparesis and diplopia were seen. But the patient fully recovered after pulse steroid therapy. Neurological examination revealed no abnormality except right hemihypoesthesia and hyperactive deep tendon reflexes. But iron deficiency aenemia deteriorated. Then, haematology and gastroenterology consultations were repeated. Celiac screening for autoantibodies antigliadin antibody (AGA) IgA and tissue transglutaminase antibody (TTG) showed positivity. Gastrointestinal endoscopy revealed antral gastritis and duodenopathy. In biopsy material, blunting of villi and intraepithelial lymphocytes was consistent with celiac disease, MARSH type 3b. The patient was given gluten-free diet for celiac disease.

MS is known to be associated with other autoimmune diseases. Since gluten sensitivity and serum antigliadin (AGA), antiendomysium (AEA), and antitissue transglutaminase (AtTGA) antibodies had been studied in MS patients, most of the studies found the prevalence of antigliadin antibodies in MS patients was the same as in controls [1, 6–9]. On the other hand, CD presents neurological dysfunctions like ataxia, peripheral neuropathy, and epilepsy. Recently “multiple sclerosis-like diseases” and headache associated with “brain MRI white-matter lesions” have been reported in celiac patients [10]. Pengiran Tengah and friends describe two cases with MS-like disease with CD. They were treated with IV methyl prednisolone for 3 days, and they were commenced on gluten-free diet [11].In our patient, intestinal symptoms were mild for years. Constipation and persistent iron deficiency did not suggest CD, and we did not perform any test for gluten sensitivity. Also, cranial and spinal lesions were not typical for MS. Multiple attacks in 1 year and no other clinical evidence for any other disease made us accept the diagnosis for MS. MRI did not show dissemination in time and space under interferon therapy.MS and CD are considered T-cell-mediated autoimmune diseases, and the involvement of Th1 cells in their pathogenesis has been suggested. Frisullo et al. reported a patient with MS and CD, and they found the interaction between MS and CD related inflammatory processes may result in an amplfication of Th1 immune response [12]. However, in CD, activated HLA-restricted gliadin-specific T cells and antigliadin antibodies are found systemically. Antigliadin antibodies are also found in the CSF. They might be responsible for headache and white-matter abnormalities as cerebellar ataxia [10].Hadjivassiliou et al. proposed that the MRI changes in their cases with MS-like disease were different than those seen in MS, being more peripherally situated and often confluent. They considered gluten sensitivity might be the etiology of “atypical” primary progressive MS particularly where ataxia is a prominent feature [13]. We describe our patient as an uncommon coincidence of MS and CD. Also, she can be diagnosed as having gluten sensitivity and MS-like disease associated with CD. We emphasize the importance of systemic examination and medical history. MS patients with gastroenterological complaints should be tested for gluten sensitivity. We suggest that the interferon therapy in MS-CD patients should also be considered with gluten-free diet.


Intestinal T-cell Responses in Celiac Disease – Impact of Celiac Disease Associated Bacteria

PLoS ONE 8(1): e53414. doi:10.1371/journal.pone.0053414

Veronika Sjöberg, Olof Sandström, Maria Hedberg, Sten Hammarström, Olle Hernell, Marie-Louise Hammarström

A hallmark of active celiac disease (CD), an inflammatory small-bowel enteropathy caused by permanent intolerance to gluten, is cytokine production by intestinal T lymphocytes. Prerequisites for contracting CD are that the individual carries the MHC class II alleles HLA-DQ2 and/or HLA-DQ8 and is exposed to gluten in the diet. Dysbiosis in the resident microbiota has been suggested to be another risk factor for CD. In fact, rod shaped bacteria adhering to the small intestinal mucosa were frequently seen in patients with CD during the “Swedish CD epidemic” and bacterial candidates could later be isolated from patients born during the epidemic suggesting long-lasting changes in the gut microbiota. Interleukin-17A (IL-17A) plays a role in both inflammation and anti-bacterial responses. In active CD IL-17A was produced by both CD8+ T cells (Tc17) and CD4+ T cells (Th17), with intraepithelial Tc17 cells being the dominant producers. Gluten peptides as well as CD associated bacteria induced IL-17A responses in ex vivo challenged biopsies from patients with inactive CD. The IL-17A response was suppressed in patients born during the epidemic when a mixture of CD associated bacteria was added to gluten, while the reverse was the case in patients born after the epidemic. Under these conditions Th17 cells were the dominant producers. Thus Tc17 and Th17 responses to gluten and bacteria seem to pave the way for the chronic disease with interferon-γ-production by intraepithelial Tc1 cells and lamina propria Th1 cells. The CD associated bacteria and the dysbiosis they might cause in the resident microbiota may be a risk factor for CD either by directly influencing the immune responses in the mucosa or by enhancing inflammatory responses to gluten.


Endocrine manifestations of celiac disease

Indian J Endocr Metab 2012;16:506-8

R Philip, PP Patidar, S Saran, P Agarwal, TVS Arya, KK Gupta

Background: Celiac disease can have extra gastrointestinal tract (GIT) presentations, most of which are endocrine. The aim of this study was to present patients diagnosed to have celiac disease from an endocrine department and to study the prevalence of endocrinopathies in celiac disease.
Materials and Methods: A total of 36 patients from the endocrinology department (LLRM Medical College, Meerut) between January 2011 and July 2012 and who were diagnosed to have celiac disease were included in the study.
Results: Short stature was the commonest presentation (25%), other presentations included short stature and delayed puberty (20%), delayed puberty (11%), screening for celiac disease in type-1 DM patients (17%), rickets (6%), anemia not responding to oral therapy (6%), type-1 DM with recurrent hypoglycaemia (6%), and osteomalacia (3%). The endocrine manifestations include (after complete evaluation) short stature (58%), delayed puberty (31%), elevated alkaline phospahatase (67%), low calcium (22%), X-rays suggestive of osteomalacia or rickets (8%), capopedal spasm (6%), and night blindness (6%). Anti-TPO antibody positivity was found in 53%, hypothyroidism in 28%, subclinical hypothyroidism in 17%, and type-1 DM in 25% of the patients. A total of 14% patients had no GI symptoms.
Conclusion: Celiac disease is an endocrine disrupter as well as the great masquerader having varied presentations including short stature, delayed puberty, and rickets. Some patients who have celiac disease may not have any GI symptoms, making the diagnosis all the more difficult. Also, there is significant incidence of celiac disease with hypothyroidism and type-1 DM, making screening for it important in these diseases.


Wellbeing, illness perception and coping strategies in Italian Celiac patients

Int J Immunopathol Pharmacol. 2012 Oct-Dec;25(4):1175-82.

Baiardini I, Braido F, Menoni S, Bellandi G, Savi E, Canonica GW, Macchia D.

The clinical features of Celiac Disease (CD) are heterogeneous and both severity and extent of villous atrophy do not correlate with clinical presentation. This study aims to evaluate the psychological wellbeing of CD patients with a similar clinical pattern and to explore whether patients with different levels of wellbeing differed in illness perception and coping strategies. CD outpatients with proven diagnosis filled in validated questionnaires to investigate wellbeing (PGWBI), illness perception (IPQ-R) and coping style (COPE). One hundred and four patients underwent data analysis. Compared to Italian reference sample, CD patients reported a significantly reduced PGWBI total score (p<0.001), self-control (p<0.001), general health (p=0.002) and vitality (p<0.001) and increased anxiety (p=0.009). 7.7% of patients reported a positive wellbeing, 40.4% distress absence, 28.8% a moderate distress and 23.1% a severe distress. Patients with distress showed a different illness perception and reported more frequently two dysfunctional strategies: focus on and venting emotions (p= 0.009) and substance abuse (p= 0.01) compared to those having a positive wellbeing. A high percentage of CD patients experience distress and differ from those who reach wellbeing in illness perception and use of coping strategies. Assessing subjective viewpoint with standardized methods can provide useful information for a better management of CD patients.


Clinical pattern of celiac disease in a population residing in North Sardinia (Italy)

Recenti Prog Med. 2012 Dec;103(12):564-9. doi: 10.1701/1206.13357.

Maria Pina Dore, Marianna Cuccu, Gianni Mario Pes, Laura Mameli, Alessandra Manca, Gian Paolo Vidili, Eugenia Togniotti

La malattia celiaca (MC) è stata per la prima volta descritta da Areteo di Cappadocia nel II secolo d.C. Il drammatico quadro clinico dei pazienti con diarrea profusa, malassorbimento, calo ponderale, grave anemia, neuropatia ed osteopenia è attualmente sostituito, nella maggior parte dei pazienti, da sintomi atipici o da una clinica silente. Quando non diagnosticata e non trattata, la MC si associa ad una elevata morbilità e mortalità.
Allo scopo di raccogliere informazioni sulle modalità di presentazione della MC nel Nord Sardegna sono stati raccolti i dati relativi a 287 pazienti con diagnosi di MC, confermata all’esame istologico. La MC è stata preponderante nelle donne (87%). Il 78,2% dei pazienti ha mostrato rispettivamente segni/sintomi classici, il 53,2% subclinici o atipici ed il 44,7% non gastrointestinali. L’anemia è stata il segno di presentazione più frequente (53%). La diarrea è stata lamentata dal 41,5% dei pazienti, e mai grave.
In conclusione, nel Nord Sardegna viene osservata con maggior frequenza una significativa proporzione di pazienti con sintomi atipici come l’anemia, piuttosto che sintomi tipici come la diarrea. Riconoscere i sintomi atipici può essere il passo più importante nella diagnosi della MC, del suo trattamento e della prevenzione delle complicanze.

Celiac disease (CD) was first described by Aretaeus from Cappadocia in II century after C. The impressive clinical picture of a patient with life-threatening diarrhea, malabsorption, weight loss, neurologic disorders and osteopenia is now often replaced by the mostly atypical symptoms or an asymptomatic presentation. When unrecognized and untreated, the celiac disease is associated with increased mortality. In order to collect information on the clinical presentation of celiac disease in North Sardinia, Italy, data on 287 patients with biopsy examination-proven celiac disease were obtained. Women predominated (87%). Overall 78,2%, 53,2% and 44,7% of patients showed classical, subclinical/silent or atypical, and no gastrointestinal features of celiac disease, respectively. Anemia was the main mode of presentation, occurring in 53% of patients. Diarrhea was less frequent (41,5%), although never severe. In conclusion, in North Sardinia a significant proportion of patients with CD are seen more commonly with non-diarrheal presentations than those with diarrhea. To recognize atypical symptoms could be the most important step in the diagnosis and further treatment.


Prevalence of Irritable Bowel Syndrome-type Symptoms in Patients With Celiac Disease: A Meta-analysis

Clin Gastroenterol Hepatol. 2012 Dec 13.

Sainsbury A, Sanders DS, Ford AC.

Patients with celiac disease (CD) often report symptoms compatible with irritable bowel syndrome (IBS). However, the prevalence of these symptoms in patients with CD and their relation to adherence to a gluten-free diet (GFD) have not been assessed systematically.
We searched MEDLINE, EMBASE, and EMBASE Classic (through July 2012) to identify cross-sectional surveys or case-control studies reporting prevalence of IBS-type symptoms in adult patients (≥16 years old) with established CD. The number of individuals with symptoms meeting criteria for IBS was extracted for each study, according to case or control status and adherence to a GFD. Pooled prevalence and odds ratios (ORs), with 95% confidence intervals (CIs), were calculated. We analyzed data from 7 studies with 3383 participants.
The pooled prevalence of IBS-type symptoms in all patients with CD was 38.0% (95% CI, 27.0%-50.0%). The pooled OR for IBS-type symptoms was higher in patients with CD than in controls (5.60; 95% CI, 3.23-9.70). In patients who were nonadherent with a GFD, the pooled OR for IBS-type symptoms, compared with those who were strictly adherent, was 2.69 (95% CI, 0.75-9.56). There was also a trend toward a higher OR for IBS-type symptoms among patients who did not adhere to the GFD, compared with controls (12.42; 95% CI, 6.84-11.75), compared with that observed for adherent CD patients vs controls (4.28; 95% CI, 1.56-11.75).
IBS-type symptoms occur frequently in patients with CD and are more common than among controls. Adherence to a GFD might be associated with a reduction in symptoms.


The Oral Manifestations of Celiac Disease: Information for the Pediatric Dentist

Pediatric Dentistry, Volume 34, Number 7, November/December 2012 , pp. 485-488(4)

Ferraz, Eduardo Gomes; Campos, Elisângela de Jesus; Sarmento, Viviane Almeida; Silva, Luciana Rodrigues

Purpose: The purpose of this article was to present a literature review of oral manifestations reported by celiac disease patients.
Methods: A review of the published literature for oral manifestations present in celiac disease patients was conducted from the following databases: PubMed®; MEDLINE; Web of Science; Science Direct; and Scielo.
Results: According to some literature studies, prevalence of enamel defects and recurrent aphthous stomatitis was observed in approximately 10% to 96% and 4% to 41% of 2- to 86-year-old celiac patients, respectively.
Conclusion: The presence of these clinical features in children may signal the need for early investigation of possible celiac disease, especially in asymptomatic cases.


Are Transglutaminase 2 Inhibitors Able to Reduce Gliadin-Induced Toxicity Related to Celiac Disease? A Proof-of-Concept Study

Journal of clinical immunology 2013, vol. 33, no1, pp. 134-142

Rauhavirta Tiina; Oittinen Mikko; Kivistö Rami; Männistö Pekka T.; Garcia-Horsman J. Arturo; Wang Zhuo; Griffin Martin; Mäki Markku; Kaukinen Katri; Lindfors Katri

Celiac disease is an autoimmune-mediated enteropathy characterized by adaptive and innate immune responses to dietary gluten in wheat, rye and barley in genetically susceptible individuals. Gluten-derived gliadin peptides are deamidated by transglutaminase 2 (TG2), leading to an immune response in the small-intestinal mucosa. TG2 inhibitors have therefore been suggested as putative drugs for celiac disease. In this proof-of-concept study we investigated whether two TG2 inhibitors, cell-impermeable R281 and cell-permeable R283, can prevent the toxic effects of gliadin in vitro and ex vivo.
Intestinal epithelial Caco-2 cells were treated with peptic-tryptic-digested gliadin (PT-gliadin) with or without TG2 inhibitors and thereafter direct toxic effects (transepithelial resistance, cytoskeletal rearrangement, junction protein expression and phoshorylation of extracellular-signal-regulated kinase 1/2) were determined. In an organ culture of celiac-patient-derived small-intestinal biopsies we measured secretion of TG2-autoantibodies into the culture medium and the densities of CD25- and interleukin (IL) 15-positive cells, forkhead box P3 (FOXP3)-positive regulatory T cells (Tregs) and Ki-67-positive proliferating crypt cells.
Both TG2 inhibitors evinced protective effects against gliadin-induced detrimental effects in Caco-2 cells but the cell-impermeable R281 seemed slightly more potent. In addition, TG2 inhibitor R281 modified the gluten-induced increase in CD25- and IL15-positive cells, Tregs and crypt cell proliferation, but had no effect on antibody secretion in celiac-patient-derived biopsies.
Our results suggest that TG2 inhibitors are able to reduce certain gliadin-induced effects related to responses in vitro and ex vivo.


Association Between Celiac Disease and Iron Deficiency in Caucasians, but not Non-Caucasians

Clinical Gastroenterology and Hepatology

Joseph A. Murray, Stela McLachlan, Paul C. Adams, John H. Eckfeldt, Chad P. Garner, Chris D. Vulpe, Victor R. Gordeuk, Tricia Brantner, Catherine Leiendecker-Foster, Anthony A. Killeen, Ronald T. Acton, Lisa F. Barcellos, Debbie A. Nickerson, Kenneth B. Beckman, Gordon D. McLaren, Christine E. McLaren

Background & Aims
Celiac disease is an increasingly recognized disorder in Caucasian populations of European origin. Little is known about its prevalence in non-Caucasians. Although it is thought to be a cause of iron deficiency anemia, little is known about the extent to which celiac disease contributes to iron deficiency in Caucasians, and especially non-Caucasians. We analyzed samples collected from participants in the Hemochromatosis and Iron Overload Screening (HEIRS) study to identify individuals with iron deficiency and assess the frequency of celiac disease.
We analyzed serum samples from white men (25 y old or older) and women (50 y old or older) who participated the HEIRS study; cases were defined as individuals with iron deficiency (serum level of ferritin ≤12 mg/L) and controls were those without (serum level of ferritin >100 mg/L in men and >50 mg/L in women). All samples were also analyzed for human recombinant tissue transglutaminase immunoglobulin A; positive results were confirmed by an assay for endomysial antibodies. Patients with positive results from both celiac disease tests were presumed to have untreated celiac disease, and those with a positive result from only 1 test were excluded from analysis. We analyzed HLA genotypes and frequencies of celiac disease between Caucasians and non-Caucasians with iron deficiency.
Celiac disease occurred in 14 of 567 of cases (2.5%) and in only 1 of 1136 controls (0.1%; Fisher’s exact test, P=1.92 10-6). Celiac disease was more common in Caucasian cases (14/363, 4%) than non-Caucasian cases (0/204; P=.003). Only 1 Caucasian control and no non-Caucasian controls had celiac disease. The odds of celiac disease in individuals with iron deficiency was 28-fold (95% confidence interval, 3.7–212.8) that of controls; 13/14 cases with celiac disease carried the DQ2.5 variant of the HLA genotype.
Celiac disease is associated with iron deficiency of Caucasians. Celiac disease is rare among non-Caucasians—even among individuals with features of celiac disease, such as iron deficiency. Celiac disease is also rare among individuals without iron deficiency. Men and post-menopausal women with iron deficiency should be tested for celiac disease.


Oral Health Status and Salivary Properties in Relation to Gluten Free Diet in Children with Celiac Disease

Journal of Pediatric Gastroenterology & Nutrition: 10 February 2013

Shetyer, Eyal; Berson, Tamar; Lachmanovitz, Odelia; Hidas, Ariela; Wilschanski, Michael; Menachem, Moti; Shachar, Edna; Shapira, Joseph; Steinberg, Doron; Moskovitz, Moti

Background: Patients with Celiac Disease (CD) have a wide variety of symptoms, from being asymptomatic to having chronic diarrhea, abdominal pain and extra-intestinal symptoms. In the oral cavity, enamel defects and recurrent aphthous stomatitis are the most common symptoms.
Aim: To assess oral health, bacterial colonization and salivary buffering capacity of patients with CD at diagnosis were compared with CD patients on gluten free diet (GFD) and healthy children.
Methods: Three groups were prospectively investigated: newly diagnosed celiac disease, celiac disease treated with GFD and a control group. All children were examined by pediatric dentists and saliva samples were collected for bacterial and pH analysis.
Result: Ninety children were enrolled in the study, thirty in each group. A higher prevalence of enamel hypoplasia (66%) was found in celiac children. Plaque Index was significantly lower in the celiac treated group, which correlated with oral health behavior: teeth brushing and frequency of eating between meals. Children on GFD brushed their teeth and used fluoride significantly more often than other children in the study. No difference between groups was found in snacks consumption, Mutans Streptococci and Lactobacilli counts in saliva, as well as pH and buffer capacity,
Conclusions: A lower degree of plaque was found in celiac children on GFD. This finding could not be explained by salivary properties or bacteria, but rather by better oral hygiene. The results should raise the awareness of pediatric gastroenterologists to oral health related issues in children with CD.


Impact of Coexistent Celiac Disease on Phenotype and Natural History of Inflammatory Bowel Diseases

Am J Gastroenterol 19 February 2013; doi: 10.1038/ajg.2013.20

Emily C Oxford, Deanna D Nguyen, Jenny Sauk, Joshua R Korzenik, Vijay Yajnik, Sonia Friedman and Ashwin N Ananthakrishnan

OBJECTIVES: Inflammatory bowel disease (IBD) and celiac disease are the two most common immune-mediated gastrointestinal diseases. There is limited knowledge regarding the course of IBD in those with coexisting celiac disease. We conducted this study to determine whether patients with coexisting celiac disease present a unique phenotype of IBD and to examine the frequency of co-occurrence of celiac disease and IBD in comparison with other autoimmune disorders.
METHODS: This was a case–control study performed at two tertiary referral centers. Cases comprised of patients with known diagnoses of celiac disease and IBD. Two random IBD controls without celiac disease were selected for each case after matching for IBD type. Disease phenotype and natural history for both Crohn’s disease (CD) and ulcerative colitis (UC) were noted from medical record review, and were compared between IBD patients with and without celiac disease.
RESULTS: We identified a total of 51 patients with IBD (22 UC, 1 indeterminate colitis, 28 CD) and celiac disease. There was no significant difference in the age, gender, or ethnicity between celiac-IBD and controls. Pancolitis was more common in celiac-UC patients as compared with controls (odds ratio (OR) 3.30, 95% confidence interval (CI) 1.05–21.50). There was also a trend toward increased use of immunomodulators (IMMs) among celiac-UC patients than in non-celiac UC controls (OR 2.83, 95% CI 0.95–8.48). No phenotypic differences were found in celiac-CD patients. There were no significant differences in IBD-related medication usage, hospitalizations, or surgeries.
CONCLUSIONS: Patients with UC and celiac disease were more likely to have pancolitis and had a trend toward greater use of IMMs. Coexisting celiac disease did not influence natural history of CD.


Prevalence of Childhood Celiac Disease and Changes in Infant Feeding

Pediatrics. 2013 Mar;131(3):e687-94.

Anneli Ivarsson, Anna Myléus, Fredrik Norström, Maria van der Pals, Anna Rosén, Lotta Högberg, Lars Danielsson, Britta Halvarsson, Solveig Hammarroth, Olle Hernell, Eva Karlsson, Lars Stenhammar, Charlotta Webb, Olof Sandström, Annelie Carlsson

OBJECTIVES: Between 1984 and 1996, Sweden experienced an “epidemic” of clinical celiac disease in children METHODS: A 2-phase cross-sectional screening study was performed in which 13 279 children from 2 birth cohorts participated: children born during the epidemic (1993) and children born after the epidemic (1997). Previously diagnosed cases were reported and confirmed. Blood samples were analyzed for serological markers and children with positive values were referred for small intestinal biopsy. Infant feeding practices in the cohorts were ascertained via questionnaires. Prevalence comparisons were expressed as prevalence ratios.
RESULTS: The total prevalence of celiac disease was 29 in 1000 and 22 in 1000 for the 1993 and 1997 cohorts, respectively. Children born in 1997 had a significantly lower risk of having celiac disease compared with those born in 1993 (prevalence ratio: 0.75; 95% confidence interval: 0.60–0.93; P = .01). The cohorts differed in infant feeding (specifically, in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding).
CONCLUSIONS: A significantly reduced prevalence of celiac disease in 12-year-olds indicates an option for disease prevention. Our findings suggest that the present infant feeding recommendation to gradually introduce gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding, is favorable.


Duodenal bulb biopsy in children for the diagnosis of coeliac disease: Experience from Perth, Australia

Journal of Paediatrics and Child Health – © 2013

Ajay Sharma, Cathy Mews, Gareth Jevon, Madhur Ravikumara

The study aims to assess the usefulness of duodenal bulb biopsy in the diagnosis of coeliac disease (CD) in a paediatric population.
Since February 2009, in our institution, we have routinely included duodenal bulb biopsy in addition to distal duodenal biopsies in children undergoing diagnostic upper gastrointestinal endoscopy. All children diagnosed with CD between February 2009 and May 2011 were identified, and those children who had biopsy finding of CD limited to duodenal bulb were reviewed with regard to clinical, serological and histopathological parameters. Duodenal bulb biopsy reports of those children who did not have CD were also reviewed as control group.
A total of 101 children were diagnosed with CD during the study period. The mean age was 8.21 years (±3.63), 33 males and 68 females. There were 8 out of 101 (7.92%) who had histological changes consistent with CD exclusively in the duodenal bulb, with normal histology in the distal duodenum. None of duodenal bulb biopsy was abnormal in the control group.
In some children, diagnostic CD changes may be limited to the duodenal bulb only and hence we recommend that duodenal bulb biopsies be included routinely in children suspected with CD to improve the diagnostic yield.


Meta-Analysis: Pediatric Celiac Disease, Cryptogenic Hypertransaminasemia, and Autoimmune Hepatitis

Journal of Pediatric Gastroenterology & Nutrition: 22 February 2013

Vajro, Pietro; Paolella, Giulia; Maggiore, Giuseppe; Giordano, Giuseppe

Objective: The association between celiac disease (CeD) and liver disease in pediatrics is well recognized, but its prevalence is unknown. This study aims to conduct a systematic review and meta-analysis to evaluate the prevalence of CeD in children with cryptogenic persistent hypertransaminasemia (HTS) or autoimmune hepatitis (AIH), and vice-versa.
Methods: We searched MEDLINE/PubMed, the Cochrane Library, Web of Science, and MD consult from 1977 to May 2012 for studies reporting either CeD and HTS or AIH. Pooled prevalences with 95% confidence intervals (CI) and relative risk (RR) were calculated.
Results: Nine studies (2046 patients) were identified. Pooled prevalences of CeD in children with mild, non-specific cryptogenic persistent HTS and vice-versa were 12.0% (95% CI 4.17-29.96) and 36.0% (95% CI 32.15-40.11), respectively. A gluten-free diet normalized transaminase levels in 77%-100% of CeD patients within 4-8 months. Pooled prevalences of CeD in children with AIH and vice-versa were 6.3% (95% CI 3.87-11.73) and 1.4% (95% CI 0.84-2.15), respectively. The RR of HTS in children with CeD versus the general population, and of CeD in children with HTS was 6.55 (95% CI 5.65-7.60) and 11.59 (95% CI 3.80-35.33), respectively. The corresponding RRs of AIH in children with CeD were 188.54 (95% CI 92.23-385.43). The RR of CeD in children with AIH was 6.63 (95% CI 3.86-11.40).
Conclusions: CeD is associated with elevated transaminase levels in about one-third of newly diagnosed children. Cryptogenic persistent HTS may signal gluten-dependent non-specific mild hepatitis (12.0% of cases) or more rarely (6.3%) severe CeD-related autoimmune hepatopathy. RRs confirm these trends in the considered associations.


Are “Gluten-Free” Foods Really Gluten-Free?

Clinical Nutrition, March 2013 – Volume 39 – Issue 3 – p 7–8

Lomangino, Kevin


Increased Risk of IgA Nephropathy Among Individuals With Celiac Disease

Journal of Clinical Gastroenterology, 24 February 2013

Welander Adina; Sundelin Birgitta; Fored Michael; Ludvigsson Jonas

Goal: To determine the risk of future biopsy-verified IgA nephropathy (IgAN) among individuals with biopsy-verified celiac disease (CD).
Background: Individuals with CD suffer increased risk of end-stage renal disease. An association between CD and IgAN has been suggested; however, results have been inconclusive and no previous study has considered the risk of IgAN in biopsy-verified CD.
Study: We performed a population-based prospective cohort study. We identified 27,160 individuals with CD (Marsh stage III) and no previous renal disease through small-intestinal biopsy reports obtained between July 1969 and February 2008 in all (n=28) Swedish pathology departments. Individuals with IgAN were identified by biopsy reports acquired at the 4 Swedish pathology departments specialized in renal pathology. Cox regression analysis was used to determine the risk of future IgAN among individuals with CD compared with 133,949 age-matched and sex-matched reference individuals.
Results: Seven (0.026%) individuals with CD and 11 (0.008%) reference individuals developed IgAN. We found an increased risk of biopsy-verified IgAN among individuals with CD [hazard ratio, 3.03; 95% confidence interval, 1.22-7.56]. The risk increase remained statistically significant after adjustment for prior liver disease and country of birth.
Conclusions: Individuals with CD suffer a 3-fold increased risk of future IgAN. Our findings warrant awareness of renal function in individuals with CD.



Celiac disease

2013 John Wiley & Sons A/S

Edgardo Rivera, Asaad Assiri, Stefano Guandalini

Celiac disease, with a prevalence around 1% of the general population, is the most common genetically-induced food intolerance in the world. Triggered by the ingestion of gluten in genetically predisposed individuals, this enteropathy may appear at any age, and is characterized by a wide variety of clinical signs and symptoms. Among them, gastrointestinal presentations include chronic diarrhea, abdominal pain, weight loss or failure to thrive in children; but extra-intestinal manifestations are also common, and actually appear to be on the rise. They include a large variety of ailments, such as dermatitis Herpetiformis, anemia, short stature, osteoporosis, arthritis, neurologic problems, unexplained elevation of transaminases, and even female infertility. For the clinician interested in oral diseases, celiac disease can lead to delayed tooth eruption, dental enamel hypoplasia, recurrent oral aphthae. Diagnosing celiac disease requires therefore a high degree of suspicion followed by a very sensitive screening test: serum levels of the autoantibody anti-tissue transglutaminase. A positive subject will then be confirmed by an intestinal biopsy, and will then be put on a strict gluten-free diet, that in most cases will bring a marked improvement of symptoms. Newer forms of treatment which in the future will probably be available to the non-responsive patients are currently being actively pursued.


Patient-centric care: Managing celiac disease

Indian J Endocr Metab [serial online] 2013 [cited 2013 Mar 6];17:177.

Bhutani J, Bhutani S, Kumar J.


Increasing prevalence and high incidence of celiac disease in elderly people: A population-based study

BMC Gastroenterology 2009, 9:49

Anitta Vilppula, Katri Kaukinen, Liisa Luostarinen, Ilkka Krekelä, Heikki Patrikainen, Raisa Valve, Markku Mäki and Pekka Collin

Background. Celiac disease may emerge at any age, but little is known of its appearance in elderly people. We evaluated the prevalence of the condition in individuals over 55 years of age, and determined the incidence of biopsy-proven celiac disease (CDb) and celiac disease including seropositive subjects for anti-tissue transglutaminase antibodies (CDb+s).
Methods. The study based on prevalence figures in 2815 randomly selected subjects who had undergone a clinical examination and serologic screening for celiac disease in 2002. A second screening in the same population was carried out in 2005, comprising now 2216 individuals. Positive tissue transglutaminase antibodies were confirmed with small bowel biopsy.
Results. Within three years the prevalence of CDb increased from 2.13 to 2.34%, and that of CDb+s from 2.45 to 2.70%. Five new cases were found among patients previously seronegative; two had minor abdominal symptoms and three were asymptomatic. The incidence of celiac disease in 2002–2005 was 0.23%, giving an annual incidence of 0.08% in this population.
Conclusion. The prevalence of celiac disease was high in elderly people, but the symptoms were subtle. Repeated screening detected five biopsy-proven cases in three years, indicating that the disorder may develop even in the elderly. Increased alertness to the disorder is therefore warranted.


Effect of B vitamin supplementation on plasma homocysteine levels in celiac disease

World J Gastroenterol 2009 February 28; 15(8): 955-960

Muhammed Hadithi, Chris JJ Mulder, Frank Stam, Joshan Azizi, J Bart A Crusius, Amado Salvador Peña, Coen DA Stehouwer, Yvo M Smulders

AIM: To investigate the effect of vitamin supplements on homocysteine levels in patients with celiac disease.
METHODS: Vitamin B6, folate, vitamin B12, and fasting plasma homocysteine levels were measured in 51 consecutive adults with celiac disease [median (range) age 56 (18-63) years; 40% men, 26 (51%) had villous atrophy, and 25 (49%) used B-vitamin supplements] and 50 healthy control individuals matched for age and sex. Finally, the C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) was evaluated in 46 patients with celiac disease and all control individuals.
RESULTS: Patients with celiac disease and using vitamin supplements had higher serum vitamin B6 (P = 0.003), folate (P < 0.001), and vitamin B12 (P = 0.012) levels than patients who did not or healthy controls (P = 0.035, P < 0.001, P = 0.007, for vitamin B6, folate, and vitamin B12, respectively). Lower plasma homocysteine levels were found in patients using vitamin supplements than in patients who did not (P = 0.001) or healthy controls (P = 0.003). However, vitamin B6 and folate, not vitamin B12, were significantly and independently associated with homocysteine levels. Twenty-four (48%) of 50 controls and 23 (50%) of 46 patients with celiac disease carried the MTHFR thermolabile variant T-allele (P = 0.89).
CONCLUSION: Homocysteine levels are dependent on Marsh classification and the regular use of B-vitamin supplements is effective in reduction of homocysteine levels in patients with celiac disease and should be considered in disease management.


A Report on the International Transglutaminase Autoantibody Workshop for Celiac Disease

Am J Gastroenterol 2009; 104:154–163; doi:10.1038/ajg.2008.8

Marcella Li, Liping Yu, Claudio Tiberti, Margherita Bonamico, Iman Taki, Dongmei Miao, Joseph A Murray, Marian J Rewers, Edward J Hoffenberg, Daniel Agardh, Patricia Mueller, Martin Stern, Ezio Bonifacio and Edwin Liu.

OBJECTIVES: Measurement of transglutaminase autoantibodies (TGAA) is considered to be the most efficient single serologic test for celiac disease (CD) by the American Gastroenterological Association Institute. We hypothesized that a large international collaborative effort toward improving and standardizing TGAA measurement is both feasible and necessary. The primary aim of this workshop is to compare TGAA assays among various research and clinical laboratories to examine assay concordance and improve (and eventually standardize) the TGAA assay.
METHODS: A total of 20 laboratories (5 commercial laboratories, 15 research and clinical laboratories) participated that included enzyme-linked immunosorbent assay (ELISA) and radiobinding assays. A total of 150 serum samples were distributed to each laboratory, with each laboratory receiving an equal aliquot that was coded and blinded, composed of 100 healthy control sera and 50 CD sera.
RESULTS: Laboratory sensitivity ranged from 69% to 93% and specificity ranged from 96% to 100%. By receiver operator characteristic analysis, the area under the curve (C index) ranged from 0.9488 to 0.9904. When analyzing for linear correlation, r-squared was as high as 0.8882 but as low as 0.4244 for the celiac samples between different laboratories performing ELISA.
CONCLUSIONS: This transglutaminase autoantibody workshop allows for larger-scale international participation for the purposes of improving and eventually standardizing the TGAA assay with subsequent workshops.

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