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  • Jefferson Adams
    Jefferson Adams

    How to Spot Celiac Disease in Children With Tissue Transglutaminase Antibodies and Normal Duodenal Architecture?

      The team's long-term study showed 43% cumulative rates of progression to villous atrophy over the 12-year study.

    Caption: Image: CC--Andrew E. Larsen

    Celiac.com 05/16/2019 - People with potential celiac disease show positive results from blood tests for tissue transglutaminase antibodies (anti-TG2), but show no damage to the intestinal lining. Such patients are all Marsh stage 0 or 1, meaning they have healthy, normal gut mucosa.

    Clinicians are still sorting out the best way to treat these patients. To provide some answers, a team of researchers recently set out to assess risk factors for villous atrophy in children with potential celiac disease.

    The team included R. Auricchio, R. Mandile, M.R. Del Vecchio, S. Scapaticci, M. Galatola, M.A. Maglio, V. Discepolo, E. Miele, D. Cielo, R. Troncone, and L. Greco. They are variously affiliated with the Department of Translation Medical Science, Section of Pediatric, and European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy, and the Department of Medicine, University of Chicago, Chicago, IL, USA.

    For children with "potential" celiac disease who do not follow gluten-free diets, possible risk factors for villous atrophy include age at diagnosis, gamma delta lymphocytes and HLA haplotype, researchers say.

    The team conducted a prospective study of 280 children between 2–18 years old in Italy who had suspected celiac disease, and followed the children from 18 months to 12 years. Each participant had two consecutive positive results from tests for anti-TG2, tested positive for the endomysial antibody (anti-EMA), had total serum levels of IgA in the normal range, normal Marsh 0–1 duodenal condition in 5 biopsies, and HLA DQ2- or DQ8-positive haplotypes. 

    The children underwent serologic tests and clinical analyses every 6 months and a small bowel biopsy every 2 years. Two hundred ten patients of the original group were checked after 9-years. The team conducted multivariate analyses of clinical, genetic, and histologic data to spot factors associated with villous atrophy.

    The team's long-term study showed 43% cumulative rates of progression to villous atrophy over the 12-year study. The team identified factors that can be used to spot children with the highest risk for villous atrophy.  

    This approach might be used to assess whether children with suspected celiac disease should immediately start a gluten-free diet or be monitored on their regular diet.

    The takeaway, Dr. Auriccio told reporters, is that potential celiac disease affects "a very heterogenous group of patients [who]...have to be carefully managed by expert pediatric gastroenterologists."

    Studies like this one by Dr. Auriccio and his team are highly valuable, because diagnosing and properly treating celiac disease as early as possible is important in helping to prevent the development of associated conditions later on.

    Read more at Gastrojournal.org


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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, science, and advanced research, and scientific methods. He previously served as Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Jefferson Adams
    Celiac.com 07/01/2013 - Potential celiac disease (PCD) is a type of celiac disease marked by positive endomysial/tissue transglutaminase antibodies and a preserved duodenal mucosa despite a gluten-containing diet (GCD). PCD can turn into active celiac disease, but very little is currently known about what causes that to happen.
    A team of researchers recently conducted a retroactive study to better understand PCD rates and the natural history of adult patients with PCD.
    The research team included F. Biagi, L. Trotta, C. Alfano, D. Balduzzi, V. Staffieri, P.I. Bianchi, A. Marchese, C. Vattiato, A. Zilli, O. Luinetti, P. Gobbi, and G.R. Corazza of the Celiac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo and the University of Pavia in Pavia, Italy.
    For their study, the team assessed the clinical notes for all 47 patients with PCD attending our clinic between September 1999 and October 2011. They established a control group of patients with active celiac disease, randomly selected and matched for sex and date of birth.
    They then compared results for symptoms, associated diseases, familiarity, and laboratory data at diagnosis for the PCD group against results from the control group. They found that 42 of 187 celiac disease patients directly diagnosed at their center had PCD. That's 1 out of every 4.4 celiac patients, 18.3%, with a 95% confidence interval (CI) 13.3-23.4%.
    There was no difference between the two groups in terms of average age at diagnosis, laboratory data, prevalence of symptoms, associated diseases, and familiarity for celiac disease.
    Interestingly, some patients with PCD maintained a normal duodenal mucosa for many years and their symptoms spontaneously improved despite continuing to regularly consume gluten. Basically, this study indicates that potential celiac disease is not a rare and/or early form of celiac disease.
    Because of the consistency in age at diagnosis and clinical features between potential celiac disease and active celiac disease, they suggest that potential celiac disease is a separate condition that can only develop into active celiac disease, though it does not always do so.

    Source:
    Scand J Gastroenterol. 2013 May;48(5):537-42. doi: 10.3109/00365521.2013.777470.

    Jefferson Adams
    What Happens to Kids with Potential Celiac Disease Who Eat Gluten?
    Celiac.com 09/03/2014 - What’s potential celiac disease, and what happens to kids who have it and continue to eat a gluten-containing diet?
    Researchers define potential celiac disease as the presence of serum anti-tissue-transglutaminase (anti-TG2) antibodies with normal duodenal mucosa. That is, a positive blood screen, but no intestinal damage. However, not much is known about potential celiac disease because people who have it often show no obvious symptoms. Patients with potential celiac disease present some challenges for doctors trying to determine how likely it is that these patients will develop villous atrophy, the gut damage common in celiac disease patients exposed to gluten.
    A research team conducted a prospective longitudinal cohort study to follow patients with potential celiac disease up to 9 years, and explore the risk factors tied to mucosal damage. The research team included Renata Auricchio MD, PhD, Antonella Tosco MD, Emanuela Piccolo MD, Martina Galatola PhD, Valentina Izzo PhD, Mariantonia Maglio PhD, Francesco Paparo PhD, Riccardo Troncone MD, PhD, and Luigi Greco MD, PhD. They are affiliated with the Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
    For their study, the team found two hundred and ten asymptomatic children with potential celiac disease. They kept 175 of them on a gluten-containing diet. To evaluate histological, immuno-histochemical, and anti-TG2 status, they checked blood antibody levels and clinical symptoms every 6 months, and took a small bowel biopsy every two years. They also genotyped all patients for HLA and non-HLA celiac-associated genes.
    Forty-three percent of patients showed persistently elevated anti-TG2 levels, 20% became negative during follow-up, and 37% showed variations in anti-TG2 course, with many patients testing at zero anti-TG2.
    After three years of follow-up, 86% of study patients continued to have potential celiac disease. After 6 and 9 years, respectively, 73% and 67% of study patients still had normal duodenal structure.
    Individuals prone to develop mucosal damage during the test period were predominantly male, had slight mucosal inflammation at study’s start, and fit a peculiar genetic profile.
    Nine years after follow-up, a large number of patients with asymptomatic potential celiac disease showed reduced antibody production, many even showing zero production, and many of these, with persistently positive anti-TG2, showed no mucosal damage.
    Given the results of this study, and noting that the celiac population is in fact made up of numerous individuals with diverse genetic and phenotypic makeup, the researchers are advising doctors to be cautious in prescribing a strict lifelong gluten-free diet for asymptomatic individuals with potential celiac disease.
    Source:
     The American Journal of Gastroenterology

    Jefferson Adams
    Celiac.com 06/10/2016 - Do all patients with potential celiac disease need a gluten-free diet? The transformation of potential celiac disease to full-blown celiac disease has been described in some western clinical studies, but there is no good data on cases in Asia.
    Recently, a team of researchers set out to study the short-term histological course of potential celiac disease in Indian patients. The research team included R Kondala, AS Puri, AK Banka, S Sachdeva, and P Sakhuja. They are variously affiliated with the Department of Gastroenterology and the Department of Pathology at Govind Ballabh Pant Hospital, New Delhi, India.
    For their study, the team identified prospective patients with potential celiac disease by screening relatives of celiac patients, patients with the diarrheal subtype of irritable bowel syndrome (IBS-D) and patients with iron deficiency anemia (IDA). They conducted endoscopy with duodenal biopsy on patients who tested positive for immunoglobulin A antibodies against tissue transglutaminase (IgA anti-tTG)
    Patients a Marsh-0 to Marsh-II lesion on duodenal biopsy, along with positive IgA tTG serology met the definition of celiac disease. The team retested for serology and histology at 6-month and 12 months.
    The team diagnosed 23 male and 34 female patients with potential celiac disease. Patients ranged from 4-73 years old, averaging 28.7 years. Of these 57 patients, 28 were identified by screening 192 first-degree relatives of 55 index cases of celiac disease, while the remaining 29 had either IBS-D or IDA. Duodenal biopsy showed Marsh-0, Marsh-I and Marsh-II changes in 28 celiac patients, 27 IBS-D patients, and 2 IDA patients.
    After 6 months, 12 patients became seronegative, while the remaining 45 patients continued to be seropositive at the 12-month time point. Only four patients moved to Marsh III status, while progression from Marsh-0 to either Marsh-I or Marsh-II occurred in six patients and one patient, respectively.
    Meanwhile, 14 patients with Marsh-I did show regression to Marsh-0. Of the two patients who were initially Marsh-II, one remained so upon follow up and one showed favorable regression to Marsh-0 status.
    This study shows that, even though almost 80% of the patients diagnosed have potential celiac disease continue to remain seropositive for tTG 12 months later, only 7% slipped to Marsh-III over the same time period.
    According to this team, these observations do not justify starting a gluten-free diet in all patients with potential celiac disease, in India.
    With all due respect to the research team, I wonder what would happen to these patients if they were followed over a greater time span? Would their conditions worsen? Clearly some longer term follow-up of such patients is warranted.
    Also, how many such patients would see an even greater regression of their symptoms and Marsh status if they followed a gluten-free diet? This study doesn’t tell us much about the possible benefits of a gluten-free diet in cases of potential celiac disease, just that, absent a gluten-free diet, some patients worsen and some improve.
    Source:
    United European Gastroenterol J. 2016 Apr;4(2):275-80. doi: 10.1177/2050640615594935.

    Jefferson Adams
    Celiac.com 06/01/2016 - People with potential celiac disease (PCD) have blood and genetic markers for celiac disease, but show little or no damage to the small intestinal mucosa.
    A research team recently conducted a prospective study to learn more about how the disease progresses in these individuals. The research team included U Volta, G Caio, F Giancola, KJ Rhoden, E Ruggeri, E Boschetti, V Stanghellini, and R De Giorgio. They are all affiliated with the departments of Medical and Surgical Sciences and Digestive System, Centro di Ricerca Biomedica Applicata at the University of Bologna, St Orsola-Malpighi Hospital, Bologna, Italy.
    For their study the team collected data from 59 women and 18 men, averaging 33 years of age. The patients were all diagnosed with potential celiac disease, based on blood tests and HLA type, at Bologna University in Italy from 2004 through 2013. All patients had either slight inflammation of the small intestinal mucosa, or normal mucosa.
    The team assessed clinical, laboratory, and histologic parameters at diagnosis and during a 3-year follow-up period. Forty-six female and 15 male patients, with an average age of 36 years, showed intestinal and extra-intestinal symptoms, whereas the remaining 13 female and 3 male patients, averaging 21 years of age, showed no symptoms at diagnosis.
    All subjects tested positive for immunoglobulin A endomysial antibody and tissue transglutaminase antibody, except for 1 patient with immunoglobulin A deficiency; 95% of patients carried the HLA-DQ2 gene. Duodenal biopsies showed that 26% of patients had a Marsh score of 0, while 74% had a Marsh score of 1.
    Thirty-six percent of symptomatic patients had autoimmune disorders, and 41% had antinuclear antibodies, compared to just 5% and 12% asymptomatic patients, respectively. Symptomatic patients were generally older at diagnosis (P < .05).
    Gluten-free diet led to significant clinical improvement in all 61 symptomatic patients. The 16 asymptomatic patients continued on gluten-containing diets, and only 1 developed mucosal flattening; levels of anti-endomysial and tissue transglutaminase antibodies fluctuated in 5 of these patients or became undetectable.
    This 3-year study of adults with potential celiac disease shows that most do have symptoms, which improved on gluten-free diet. However, asymptomatic adults with potential celiac disease do not tend to develop villous atrophy, and so do not require treatment with a gluten-free diet.
    Source:
    Clin Gastroenterol Hepatol. 2016 May;14(5):686-693.e1. doi: 10.1016/j.cgh.2015.10.024. Epub 2015 Oct 30.

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