CELIAC DISEASE WHAT S THE LATEST? Peter HR Green MD

Transcription

1 CELIAC DISEASE WHAT S THE LATEST? Peter HR Green MD pg11@columbia.edu

2 CELIAC DISEASE Common Underdiagnosed Biopsy is the gold standard for diagnosis

3 CLINICAL FEATURES Dig Dis Sci EJGH, Sontig 2013

4 Most U.S. Patients With Celiac Disease Are Undiagnosed Seroprevalence: 0.7%-1.0% Female = male Percentage undiagnosed: Olmsted County (2001): 95% Wyoming (2003): 90% Washington County, Maryland (1989): 89% NHANES ( ): 83% Rubio-Tapia, et al. Am J Gastroenterol 2012;107: Fasano, et al. Arch Intern Med. 2003;163: Katz, et al. Am J Gastroenterol 2010; 106: Murray, et al. Clin Gastro Hep 2003;1:19-27 Catassi et al. Ann Med 2010; 42: 530-8

5 The Gluten Paradox Patients with Celiac Disease Individuals On a Gluten-Free Diet Rubio-Tapia, et al. Am J Gastroenterol 2012;107:

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7 Determined degree of adherence to guidelines and the result of adherence (>4 biopsies) Analyzed the results of biopsy specimens of 132,352 patients Only 35% of patients had 4 specimens submitted Gastrointest Endosc. 2011;74:103-9.

8 NUMBER OF SPECIMENS OF SMALL BOWEL BIOPSIES Gastrointest Endosc. 2011;74:103-9.

9 ADHERENCE ACCORDING TO INDICATION Indication % with 4 specimens OR for diagnosis of CD when 4 specimens Anemia ( ) Diarrhea ( ) Dyspepsia ( ) Heartburn ( ) Weight loss ( ) Suspected celiac disease/malabsorption ( ) Gastrointest Endosc. 2011;74:103-9.

10 CORI DATA BASE Among those with iron deficiency, anemia, weight loss or diarrhea undergoing EGD during the years (n= 13,091) Only 43% underwent small intestinal biopsy Groups that are less likely to have a biopsy: Non-white, Male, weight loss

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12 Biopsies of the bulb can be assessed for villous atrophy and intraepithelial lymphocytosis Bulb biopsies increased the yield of diagnosis by 13%

13 ULTRA SHORT CELIAC DISEASE CELIAC DISEASE CONFINED TO THE BULB Celiac patients with villous atrophy in the bulb only are younger (p=0.03), less frequently present with diarrhoea (p<0.0001), have lower ttg titres (p<0.0001), and higher folate levels (p=0.02) than in conventional celiac disease. Celiac patients with villous atrophy in the bulb appear to have milder clinical phenotype (DDW 2015 Sanders et al)

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16 BIOPSY 4 to 6 in descending duodenum 2 from bulb (increases diagnosis by 13%) 1 bite per pass of the forceps Gonzales, GIE 2010 Latorre, GIE, 2015

17 Controversial Follow-up Biopsy? Not necessary: if symptoms resolve and TTG normalizes Helpful: more sensitive than TTG in detecting gluten exposure Helpful: normal TTG does not reflect status of the mucosa Asymptomatic patients Prognostic implications?

18 Consequences of Persistent Villous Outcome Mortality (Aliment Pharmacol Ther 2013;37:332-9.) Atrophy Hazard Ratio (95% CI) 1.01 ( ) Interpretation No increased risk Ischemic Heart Disease (DDW 2014: Su1437) 0.97 ( ) No increased risk Lymphoproliferative Malignancy (Ann Intern Med 2013;159: ) 2.26 ( ) Increased risk Hip Fracture (J Clin Endocrinol Metab 2014;99: ) 1.67 ( ) Increased risk

19 REFRACTORY CELIAC DISEASE Persistent villous atrophy and symptoms despite GF diet >12 months CLASSIFICATION Based on characterization of the IELs TYPE I normal IEL phenotype CD3+, CD8+ TYPE II aberrant IEL phenotype Intracytoplasmic expression of CD3, without expression of surface T-cell markers (CD3, CD8) associated with monoclonal TCRγ gene rearrangement Cellier, Lancet 2000 Abnormal IELs are driven by IL15

20 REFRACTORY CELIAC DISEASE TYPE I good prognosis TYPE II poor prognosis progression to overt lymphoma EATL 5 year survival 40-57% We are going to be the US site for an anti IL15 therapy

21 SCREENING FOR MALIGNANCY General population Breast cancer Colon cancer Prostate (?) Celiac disease should there be additional screening for malignancy?

22 SCREENING FOR MALIGNANCY IN CELIAC DISEASE Increased risk of lymphoma Increased risk of oro-esophageal, small intestine and liver cancer No increased risk of colon cancer nor colonic adenoma No increased risk prostate cancer Reduced risk of breast, ovarian and endometrial cancer Lebwohl APT 2010 Ludvigsson Int JcCancer 2011 Ludvigsson Br J Cancer 2012

23 Total 72 Female 51.4% Mean age 59 (29-85 years) Presented w/ diarrhea 76.4% Mean time of follow up 26.4 (months) All attended the celiac center as poorly responsive celiac disease over a 10 year period

24 MEDICATION RELATED VILLOUS ATROPHY MRVA MEDICATIONS = OLMESARTAN, MECOPHENOLATE, MTX

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26 NORTH AMERICAN SOCIETY FOR THE STUDY OF CELIAC DISEASE