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  • Jefferson Adams
    Jefferson Adams

    The Use of Computed Tomography in Refractory Celiac Disease and Enteropathy-associated T-cell Lymphoma

    Celiac.com 08/17/2008 - One of the important ways doctors distinguish between the two types of refractory celiac disease is by looking at differences in intra-epithelial T lymphocytes (IELs) in intestinal biopsies. People with refractory celiac disease who show normal IELs are said to have refractory celiac disease I, while those with abnormal IELs are said to have refractory celiac disease II.

    A team of doctors based in the Netherlands recently set out to assess the effectiveness of computed tomography (CT) in diagnosing refractory celiac disease, and enteropathy-associated T-cell lymphoma (EATL). EATL is a generally rare, but particularly aggressive form of bowel cancer that is the leading cause of death in adults with celiac disease.

    The study team was made up of doctors Maarten Mallant, Muhammed Hadithi, Abdul-Baqi Al-Toma, Matthijs Kater, Maarten Jacobs, Radu Manoliu, Chris Mulder, and Jan Hein van Waesberghe.

    The team looked at 46 patients with clinically proven celiac disease, refractory celiac disease I, refractory celiac disease II, or EATL including 18 males and twenty-eight females. The first group contained 14 patients with uncomplicated celiac disease and 10 with type I refractory celiac disease. The second group contained 15 patients with type II refractory celiac disease and 7 patients with EATL. 5 patients from group II showed lymphandenopathy, compared to none in the first group. 20 patients from group I showed a higher number of small mesenteric vessels compared to just 11 from group II.

    This is significant because increased numbers of small mesenteric vessels are associated with an absence of refractory celiac disease II and EATL, while reduced numbers of small mesenteric vessels are associated with a higher rate of refractory celiac disease II and EATL.

    The team evaluated the two groups within eleven categories: abnormal intestinal fold patterns; bowel wall thickness, excess fluid; intestinal insussuction; ascites; lymphadenopathy; increases in lymph node numbers; mesenteric vascular changes; and spleen size. One other area the doctors found important was in differences in the average thickness of the bowel wall. Group I showed thinner bowel walls compared to group II. In group I, average bowel thickness ranged from 4mm to 11mm, with an average thickness of 7.0mm. In group II, average bowel thickness ranged from 5mm to 15mm, with an average thickness of 10.0mm. So, group II showed about 30% thicker bowel walls than group I.

    The doctors’ conclusions reaffirmed the need for a biopsy before confirming a diagnosis of celiac disease. Regarding the use of CT, the team found CT unnecessary for cases of uncomplicated celiac disease, but found CT very useful in cases of complicated and pre-cancerous celiac disease.

    The study team also found that pattern reversal and/or loss of jejunal folds is specific to celiac disease, though they had an admittedly small sample of just 24 of their 46 patients, so their measures are far from definitive.

    All of this drives home the importance of encouraging early and accurate screening for celiac disease. Ideally, we will get to the point where, like many European countries, we will begin to catch celiac disease before it ever becomes refractory, and before it ever develops into EATL.

    Until then, stay informed and take an active role in maintaining your own health.

    World J Gastroenterol 2007; 13(11): 1696-1700



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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 04/13/2010 - A team of clinicians recently described a case of immune modulation by non-Hodgkin lymphoma in a patient with two primary intestinal T-Cell lymphomas and long-standing celiac disease.
    F. Mühr-Wilkenshoff, M. Friedrich, H. D. Foss, M. Hummel, M. Zeitz, and S. Daum made up the research team. They are variously affiliated with the  Medical Clinic I, Gastroenterology, Rheumatology and Infectious Diseases, and with the Department of Pathology, Charité of the Campus Benjamin Franklin of University Medicine Berlin, Germany.
    About 20–30% of all non-Hodgkin lymphomas (NHLs) are gastrointestinal in nature. Of these gastrointestinal lymphomas, about 20–30% occur in small intestine
    The clinical team recently reported the case of a 72-year-old patient who had been diagnosed with celiac disease when he was 52-years old. The man had not followed a gluten-free diet, yet showed no evidence of enteropathy or celiac-associated antibodies, but still developed a jejunal T-cell lymphoma.
    Doctors resected the lymphoma due to perforation and treated the patient with four courses of IMVP-16. The patient began and maintained a strict gluten-free diet.
    Two years later, the patient appeared with weight loss and a clonally divergent refractory sprue type II with loss of antigen (CD8; T-cell receptor-) expression in intraepithelial lymphocytes.
    At this time, he showed high titers of celiac-associated antibodies, although he was on a strict GFD.
    The research team notes that the missing enteropathy under a gluten-containing diet supports the idea of immune suppression in malignant diseases, especially non-Hodgkin lymphoma.
    They also note that the fact that, even while maintaining a strict gluten-free diet, the patient developed refractory sprue type II, an early form of another independent T-cell lymphoma, along with celiac-associated antibodies, suggests that clonal intraepithelial lymphocytes might be stimulating antibody production.
    Thus, they conclude that isolated detection of celiac-associated antibodies in patients with celiac disease does not prove that patients have deviated from their gluten-free diets.
    Source:

    Digestion 2010;81:231–234 DOI: 10.1159/000269810

    Jefferson Adams
    Celiac.com 05/19/2010 - Enteropathy-associated T cell lymphoma is a serious complication of celiac disease, and a major cause of mortality in untreated celiac disease.
    One possible trigger for Enteropathy-associated T cell lymphoma development is chronic exposure of intraepithelial lymphocytes (IELs) to strong anti-apoptotic signals, that is, signals that interfere in the normal mortality of the IEL cells. These signals are triggered by IL-15, a cytokine that is over-expressed in the enterocytes of people with celiac disease.
    However, researchers have not yet fully mapped the signaling pathway by which IL-15 transmits these anti-apoptotic signals. Researchers consider type II refractory celiac disease (RCDII) to be a middle step between celiac disease and enteropathy-associated T cell lymphoma.
    Eliminating abnormal IELs at the RCDII stage would likely block EATL development. So far, though, scientists have not found successful immunosuppressive and/or chemotherapeutic approaches able to accomplish this, and RCDII outcomes remain very poor.
    A team of researchers recently set out to map the IL-15–driven survival pathway in human IELs, and to determine whether IL-15 triggered pathway in human intraepithelial lymphocytes represents a possible new target in type II refractory celiac disease and enteropathy-associated T cell lymphoma.
    The research team was made up of Georgia Malamut, Raja El Machhour, Nicolas Montcuquet, Séverine Martin-Lannerée, Isabelle Dusanter-Fourt, Virginie Verkarre, Jean-Jacques Mention, Gabriel Rahmi, Hiroshi Kiyono, Eric A. Butz, Nicole Brousse, Christophe Cellier, Nadine Cerf-Bensussan, and Bertrand Meresse.
    The are variously affiliated with INSERM U989, the Université Paris Descartes, Faculté de Médecine René Descartes, the Department of Gastroenterology, AP-HP, Hôpital Européen Georges Pompidou, the Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), INSERM U1016, the Department of Pathology, AP-HP, of the Hôpital Necker-Enfants Malades in Paris, with the Division of Mucosal Immunology, Department of Microbiology and Immunology at the Institute of Medical Science at the University of Tokyo in Japan, and the Inflammation Department of AMGEN Inc., in Seattle, Washington, USA.
    Their current findings reveal that the survival signals IL-15 directs to freshly isolated human IELs, and to human IEL cell lines derived from celiac disease patients with type II refractory celiac disease, depend on anti-apoptotic factors Bcl-2 and/or Bcl-xL.
    The signals require IL-15Rβ, Jak3, and STAT5 for proper function, but functioned independently of PI3K, ERK, and STAT3. In support of these findings, the team recorded elevated levels of Bcl-xL, phospho-Jak3, and phospho-STAT5 in IELs from patients with active celiac disease and RCDII.
    Moreover, by incubating patient duodenal biopsies with a fully humanized human IL-15–specific Ab, the team effectively blocked Jak3 and STAT5 phosphorylation.
    Also, treatment with IL-15–specific Ab caused IEL cell mortality, and wiped out the massive IEL build-up in mice over-expressing human IL-15 in their gut epithelium.
    The study marks the first successful mapping of the IL-15–driven survival pathway in human IELs, and demonstrates that IL-15 and its downstream effectors are meaningful therapeutic targets in RCDII.
    These findings will likely help to pave the way for the development of successful immunosuppressive and/or chemotherapeutic treatments that destroy abnormal IELs at the RCDII stage and help to block EATL development, improving outcomes for RCDII patients.
    Source:

    Journal of Clinical Investigation doi:10.1172/JCI41344

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    The celiac tests are: TTG IgA TTG IgG DGP IgA DGP IgG  EMA IgA And....Immunogobulin A (IgA).  This test is used only as a control test when checking for celiac disease.  If your body is not producing enough IgA, the IgA celiac tests are invalid or will not work.    You would also have a immune deficiency issues too.  But that is a separate issue.   The previous link I gave you spells out the test names which are long!  😆
    Guys, thanks so much for taking time out of your day to reply to me. I'm going to ask my doc for the test, she's super and I'm sure she will go for it. This whole thing has sure taken it's toll on me both mentally and physically the last couple of months... to be honest, I don't care if I have it or not, I just want to know what's going on
    Dziekuje bardzo for that information,, CyclingLady! And you are correct, at least in my case --- I have been EXTREMELY reluctant to eat out in restaurants since going gluten free last year, and have only done so a small handful of times, under very strict conditions and only after talking to both the serving staff and the chefs/cooks at some length.  Now, on the Fasano Diet, it is simply not an option. Honestly, I do not understand this recent mania for eating out ALL the time!  Not on
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