International Journal of Celiac Disease
ISSN (Print): 2334-3427 ISSN (Online): 2334-3486 Website: Editor-in-chief: Samasca Gabriel
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International Journal of Celiac Disease. 2017, 5(1), 14-18
DOI: 10.12691/ijcd-5-1-4
Open AccessArticle

Mucosal Recovery and Mucosal Healing in Biopsy-Defined Adult Celiac Disease

Hugh James Freeman1,

1Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, BC, Canada

Pub. Date: March 02, 2017

Cite this paper:
Hugh James Freeman. Mucosal Recovery and Mucosal Healing in Biopsy-Defined Adult Celiac Disease. International Journal of Celiac Disease. 2017; 5(1):14-18. doi: 10.12691/ijcd-5-1-4


Celiac disease (gluten-sensitive enteropathy) is an immune mediated disorder with characteristic histopathological small bowel mucosal changes that respond to a strict gluten-free diet. Recent studies have suggested that complete (rather than partial) mucosal recovery and healing is possible, but in some this may require a more prolonged period than is currently appreciated. In this study, 182 patients (60 males, 122 females) referred for evaluation of symptoms, including diarrhea and weight loss, were selected only if initial biopsies showed characteristic inflammatory changes with severe architectural disturbance. All patients were treated with a strict gluten diet alone and diet compliance regularly monitored. Up to 90% or more of patients showed a complete mucosal response or healing. A time-dependent rate of response was noted with most patients requiring more than 1 year, and even 2 years or more, to respond, however, complete mucosal healing was still possible within 6 months. In this evaluation, females in each of 4 different age ranges had mucosal response and healing rates superior to males, while elderly celiacs had lower rates. Such factors should be considered before labeling a patient with “non-responsive” disease. However, inflammatory changes with persistent architectural disturbance, especially in celiacs with a late diagnosis and resultant late initiation of a gluten-free diet treatment, may be at increased risk for a later small bowel complication, including lymphoma.

adult celiac disease mucosal healing villous atrophy intraepithelial lymphocytosis gluten-free diet

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[1]  Gujral N, Freeman HJ, Thomson AB. Celiac disease: prevalence, pathogenesis and treatment. World J Gastroenterol 2012; 18: 6036-6059.
[2]  Freeman HJ. Pearls and pitfalls in the diagnosis of adult celiac disease. Can J Gastroenterol 2008; 22: 273-280.
[3]  Perera DR, Weinstein WM, Rubin CE. Symposium on pathology of the gastrointestinal tract. Part II. Small intestinal biopsy. Hum Pathol 1975; 6: 157-217.
[4]  Lewin KJ, Riddell RH, Weinstein WM. Chapter 20. Small bowel mucosal disease. In: Gastrointestinal Pathology and its Clinical Implications. Volume 2. Igaku-Shoin, Tokyo. 1992; 750-811.
[5]  Marsh MN. Gluten, major histocompatibility complex and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (“celiac sprue”). Gastroenterology 1992; 102: 330354.
[6]  Corazza GR, Vilanacci V, Zambelli C, Millone M, Luinetti O, Vindigni C, Chioda C, Albarello L, Bartolini D, Donato T. Comparison of the intraobserver reproducibility with different histologic criteria used in celiac disease. Clin Gastroenterol Hepatol 2007; 5: 838-843.
[7]  Rostami K, Aldulaimi D, Holmes G, Johnson MW, Robert M, Srivastava A, Flejou J-F, Sanders DS, Volta U, Derakhshan MH, Going JL, Bechaneau G, Catassi C, Danciu M, Materacki L, Ghafarzadegan K, Ishaq S, Rostami-Nejad M, Pena AS, Bassotti G, Marsh MN, Villanacci V. Microscopic enteritis: Bucharest consensus. World J Gastroenerol 2015; 21: 2593-2604.
[8]  Marsh MN, Rostami K. What is normal intestinal mucosa? Gastroenterology 2016; 151; 784-788.
[9]  Freeman HJ. Refractory celiac disease and sprue-like intestinal disease. World J Gastroenterol 2008; 14: 828-830.
[10]  Freeman HJ. Drug-induced sprue-like intestinal disease. Inter J Celiac Dis 2014; 2: 49-53.
[11]  Freeman HJ. Olmesartan enteropathy. Inter J Celiac Dis 2016; 4: 24-26.
[12]  Gonzalez-Cordero PL, Fernandez-Gonzalez N, Molina-Infante J. Sprue-like enteropathy with oxcarbazepine. Am J Gastroenterol 2016; 111: 1662-1663.
[13]  Dickey W, Hughes DF, McMillan SA. Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery. Am J Gastroenterol 2000; 95: 712-714.
[14]  Kaukinen K, Sulkanen S, Maki M, Collin P. IgA-class transglutaminase antibodies in evaluating the efficacy of gluten-free diet in celiac disease. Eur J Gastroenterol Hepatol 2002; 14: 311-315.
[15]  Tursi A, Brandimarte G, Giorgetti GM. Lack of usefulness of anti-transglutaminase antibodies in assessing histologic recovery after gluten-free diet in celiac disease. J Clin Gastroenterol 2003; 37: 387-391.
[16]  Sharkey LM, Corbett G, Currie E, Lee J, Sweeney N, Woodward JM. Optimising delivery of care in celiac disease—comparison of the benefits of repeat biopsy and serological follow-up. Aliment Pharmacol Ther 2013; 38: 1278-1291.
[17]  Schmidt E, Smyrk TC, Faubion WA, Oxentenko AS. Duodenal intraepithelial lymphocytosis with normal villous architechture in pediatric patients, 2000-2009: The Mayo Clinic experience. J Pediatr Gastroenterol Nutr 2013; 56: 51-55.
[18]  Kakar S, Nehra V, Murray JA, Dayharsh GA, Burgart LJ. Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture. Am J Gastroenterol 2003; 98: 2027-2033.
[19]  Haere P, Hoie O, Schulz T, Schonhardt I, Raki Mi, Lundin KE. Long-term mucosal recovery and healing in celiac disease is the rule---not the exception. Scand J Gastroenterol 2016; 51: 1439-1446.
[20]  Freeman H, Lemoyne M, Pare P. Celiac disease in the elderly. Best Pract Res Clin Gastroenterol 2002; 16: 37-49.
[21]  Freeman HJ. Adult celiac disease in the elderly. World J Gastroenterol 2008; 14: 6911-6914.
[22]  Tursi A, Brandimarte G, Giorgetti GM, Elisei W, Inchingolo CD, Monardo E, Aiello F. Endoscopic and histological findings in the duodenum of adults with celiac disease before and after changing to a gluten-free diet: a 2-year prospective study. Endoscopy 2006; 38: 702-707.
[23]  Hutchinson JM, West NP, Robins GC, Howdle PD. Long-term histological follow-up of people with celiac disease in a UK teaching hospital. QJM 2010; 103: 511-517.
[24]  Pekki H, Kurppa K, Maki M, Huhtala H, Sievanen H, Laurila K, Collin P, Kaukinen K. Predictors and significance of incomplete mucosal recovery in celiac disease after 1 year on a gluten-free diet. Am J Gastroenterol 2015; 110: 1078-1085.
[25]  Galli G, Esposito G, Lahner E, Pilozzi E, Corleto VD, Di Giulio E, Aloe Spiriti MA, Annibale B. Histological recovery and gluten-free diet adherence: a prospective 1-year follow-up study of adult patients with celiac disease. Aliment Pharmacol Ther 2014; 40: 639-647.
[26]  Tuire I, Marja-Leena L, Teea S, Katri H, Jukka P, Paivi S, Heini H, Markku M, Pekka C, Katri K. Persistent duodenal intraepithelial lymphocytosis despite a long-term strict gluten-free diet in celiac disease. Am J Gastroenterol 2012; 107: 1563-1569.
[27]  Freeman HJ. Lymphoproliferative and intestinal malignancies in 214 patients with biopsy-defined celiac disease. J Clin Gastroenterol 2004; 38: 429-434.